NM_001122752.2(SERPINI1):c.10C>T (p.Leu4Phe) AND Familial encephalopathy with neuroserpin inclusion bodies

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001360349.7

Allele description [Variation Report for NM_001122752.2(SERPINI1):c.10C>T (p.Leu4Phe)]

NM_001122752.2(SERPINI1):c.10C>T (p.Leu4Phe)

Gene:

SERPINI1:serpin family I member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q26.1

Genomic location:

Preferred name:

NM_001122752.2(SERPINI1):c.10C>T (p.Leu4Phe)

HGVS:

NC_000003.12:g.167789138C>T
NG_008217.1:g.58495C>T
NM_001122752.2:c.10C>TMANE SELECT
NM_005025.5:c.10C>T
NP_001116224.1:p.Leu4Phe
NP_005016.1:p.Leu4Phe
NC_000003.11:g.167506926C>T

Protein change:

L4F

Links:

dbSNP: rs1483914626

NCBI 1000 Genomes Browser:

rs1483914626

Molecular consequence:

NM_001122752.2:c.10C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005025.5:c.10C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial encephalopathy with neuroserpin inclusion bodies
Synonyms:: ENCEPHALOPATHY, FAMILIAL, WITH COLLINS BODIES
Identifiers:: MONDO: MONDO:0011412; MedGen: C1858680; Orphanet: 85110; OMIM: 604218

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001556263	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001556263

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001556263.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces leucine with phenylalanine at codon 4 of the SERPINI1 protein (p.Leu4Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SERPINI1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SERPINI1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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