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NM_006922.4(SCN3A):c.1663C>A (p.Pro555Thr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 5, 2021
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:
RCV001839115.1

Allele description [Variation Report for NM_006922.4(SCN3A):c.1663C>A (p.Pro555Thr)]

NM_006922.4(SCN3A):c.1663C>A (p.Pro555Thr)

Gene:
SCN3A:sodium voltage-gated channel alpha subunit 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_006922.4(SCN3A):c.1663C>A (p.Pro555Thr)
HGVS:
  • NC_000002.12:g.165146747G>T
  • NG_042289.1:g.62342C>A
  • NM_001081676.2:c.1663C>A
  • NM_001081677.2:c.1663C>A
  • NM_006922.4:c.1663C>AMANE SELECT
  • NP_001075145.1:p.Pro555Thr
  • NP_001075146.1:p.Pro555Thr
  • NP_008853.3:p.Pro555Thr
  • NC_000002.11:g.166003257G>T
Protein change:
P555T
Links:
dbSNP: rs2105833109
NCBI 1000 Genomes Browser:
rs2105833109
Molecular consequence:
  • NM_001081676.2:c.1663C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001081677.2:c.1663C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006922.4:c.1663C>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Developmental and epileptic encephalopathy, 62
Synonyms:
Early infantile epileptic encephalopathy 62
Identifiers:
MONDO: MONDO:0033371; MedGen: C4693699; OMIM: 617938
Name:
Epilepsy, familial focal, with variable foci 4 (FFEVF4)
Identifiers:
MONDO: MONDO:0054776; MedGen: C4693694; OMIM: 617935

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002099030New York Genome Center - CSER-NYCKidSeq
criteria provided, single submitter

(NYGC Assertion Criteria 2020)		Uncertain significance
(Mar 5, 2021) 		inheritedclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedinheritedunknown1not providednot provided1not providedclinical testing

Details of each submission

From New York Genome Center - CSER-NYCKidSeq, SCV002099030.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.1663C>A (p.Pro555Thr) variant identified in the SCN3A gene substitutes a conserved Proline for Threonine at amino acid 555/2001 (exon 12/28). This variant is absent from gnomAD(v3.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.014) and Pathogenic (REVEL; score:0.637) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. This variant is within the cytoplasmic domain between transmembrane domains I and II (UniProtKB:Q9NY46). Given the lack of compelling evidence for its pathogenicity, the inherited c.1663C>A (p.Pro555Thr) variant identified in the SCN3A gene is reported as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedunknown1not providednot provided1not providednot providednot provided

Last Updated: Dec 24, 2023