rs3763695

Positions:

• chr10-100509449-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015490.4(SEC31B):​c.266T>C​(p.Val89Ala) variant causes a missense change. The variant allele was found at a frequency of 0.215 in 1,613,696 control chromosomes in the GnomAD database, including 38,253 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.21 (3389 hom., cov: 32)
  • Exomes 𝑓: 0.22 (34864 hom.)
• Consequence: SEC31B NM_015490.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.19

Genes affected

SEC31B (HGNC:23197): (SEC31 homolog B, COPII coat complex component) This gene encodes a protein of unknown function. The protein has moderate similarity to rat VAP1 protein which is an endosomal membrane-associated protein, containing a putative Ca2+/calmodulin-dependent kinase II phosphorylation site. [provided by RefSeq, Jul 2008]

ENSG00000255339 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010405183).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC31B	NM_015490.4	c.266T>C	p.Val89Ala	missense_variant	4/26	ENST00000370345.8	NP_056305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC31B	ENST00000370345.8	c.266T>C	p.Val89Ala	missense_variant	4/26	1	NM_015490.4	ENSP00000359370.3
ENSG00000255339	ENST00000557395.5	n.*324-347T>C		intron_variant		2		ENSP00000456832.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31482 AN: 151998 Hom.: 3381 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.205

GnomAD3 exomes AF: 0.206 AC: 51592 AN: 250926 Hom.: 5562 AF XY: 0.208 AC XY: 28156 AN XY: 135634

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.225

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.216 AC: 316089 AN: 1461580 Hom.: 34864 Cov.: 33 AF XY: 0.217 AC XY: 157935 AN XY: 727096

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.207 AC: 31499 AN: 152116 Hom.: 3389 Cov.: 32 AF XY: 0.208 AC XY: 15449 AN XY: 74354

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.202

Alfa AF: 0.214 Hom.: 9127

Bravo AF: 0.204

TwinsUK AF: 0.217 AC: 803

ALSPAC AF: 0.215 AC: 827

ESP6500AA AF: 0.194 AC: 856

ESP6500EA AF: 0.220 AC: 1889

ExAC AF: 0.209 AC: 25355

Asia WGS AF: 0.192 AC: 668 AN: 3478

EpiCase AF: 0.208

EpiControl AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.96	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Benign	0.43	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.19
MPC		0.037
ClinPred		0.031	T
GERP RS		5.4
Varity_R		0.035
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs3763695; hg19: chr10-102269206; COSMIC: COSV64824816; COSMIC: COSV64824816;