rs3763695

Variant names:

• chr10-100509449-A-G
• rs3763695
• NM_015490.4:c.266T>C

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015490.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC31B	NM_015490.4	MANE Select	c.266T>C	p.Val89Ala	missense	Exon 4 of 26	NP_056305.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC31B	ENST00000370345.8	TSL:1 MANE Select	c.266T>C	p.Val89Ala	missense	Exon 4 of 26	ENSP00000359370.3
	SEC31B	ENST00000479697.5	TSL:1	n.204-347T>C		intron	N/A	ENSP00000473995.1
	ENSG00000255339	ENST00000557395.5	TSL:2	n.*324-347T>C		intron	N/A	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

GnomAD2 exomes AF: 0.206 AC: 51592 AN: 250926 AF XY: 0.208

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 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

African (AFR) AF: 0.194 AC: 6480 AN: 33474

American (AMR) AF: 0.163 AC: 7271 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5204 AN: 26134

East Asian (EAS) AF: 0.178 AC: 7049 AN: 39696

South Asian (SAS) AF: 0.229 AC: 19763 AN: 86246

European-Finnish (FIN) AF: 0.233 AC: 12435 AN: 53352

Middle Eastern (MID) AF: 0.218 AC: 1256 AN: 5762

European-Non Finnish (NFE) AF: 0.219 AC: 243827 AN: 1111824

Other (OTH) AF: 0.212 AC: 12804 AN: 60380

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

African (AFR) AF: 0.202 AC: 8362 AN: 41478

American (AMR) AF: 0.180 AC: 2752 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3468

East Asian (EAS) AF: 0.144 AC: 742 AN: 5168

South Asian (SAS) AF: 0.230 AC: 1110 AN: 4818

European-Finnish (FIN) AF: 0.222 AC: 2347 AN: 10592

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14832 AN: 67992

Other (OTH) AF: 0.202 AC: 427 AN: 2110

Alfa AF: 0.214 Hom.: 12020

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 v4.9

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
PhyloP100		5.2
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
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3763695; hg19: chr10-102269206; COSMIC: COSV64824816; COSMIC: COSV64824816;