3-38761192-G-T

Position:

• chr3-38761192-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006514.4(SCN10A):​c.883C>A​(p.Pro295Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCN10A NM_006514.4 missense, splice_region
• Scores: Splicing: ADA: 0.00001773
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

Genes affected

SCN10A (HGNC:10582): (sodium voltage-gated channel alpha subunit 10) The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10165185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.883C>A	p.Pro295Thr	missense_variant, splice_region_variant	7/28	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.883C>A	p.Pro295Thr	missense_variant, splice_region_variant	7/28	1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.883C>A	p.Pro295Thr	missense_variant, splice_region_variant	6/27			ENSP00000495595.1
SCN10A	ENST00000655275.1	c.883C>A	p.Arg295Ser	missense_variant	7/28			ENSP00000499510.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449510 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720458

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	0.074
DANN	Benign	0.24
DEOGEN2	Benign	0.36	T;.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.13	.;T;T;T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.2	L;.;L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.40	N;.;.;.
REVEL	Benign	0.25
Sift	Benign	0.63	T;.;.;.
Sift4G	Benign	0.59	T;.;.;.
Polyphen		0.0010	B;.;B;.
Vest4		0.19
MutPred		0.55		Gain of glycosylation at Y298 (P = 0.0339);Gain of glycosylation at Y298 (P = 0.0339);Gain of glycosylation at Y298 (P = 0.0339);Gain of glycosylation at Y298 (P = 0.0339);
MVP		0.27
MPC		0.066
ClinPred		0.047	T
GERP RS		-7.7
Varity_R		0.039
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000018
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371909817; hg19: chr3-38802683;