rs3793706

Variant names:

• chr10-100509328-C-A
• rs3793706
• NM_015490.4:c.387G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-100509328-C-A
• chr10-100509328-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015490.4(SEC31B):​c.387G>T​(p.Leu129Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,612,694 control chromosomes in the GnomAD database, including 39,189 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.22 (3841 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35348 hom.)
• Consequence: SEC31B NM_015490.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• Publications: 42 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=0.0019181669).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC31B	NM_015490.4	MANE Select	c.387G>T	p.Leu129Phe	missense	Exon 4 of 26	NP_056305.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC31B	ENST00000370345.8	TSL:1 MANE Select	c.387G>T	p.Leu129Phe	missense	Exon 4 of 26	ENSP00000359370.3
	SEC31B	ENST00000479697.5	TSL:1	n.204-226G>T		intron	N/A	ENSP00000473995.1
	ENSG00000255339	ENST00000557395.5	TSL:2	n.*324-226G>T		intron	N/A	ENSP00000456832.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33487 AN: 151882 Hom.: 3830 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.218

GnomAD2 exomes AF: 0.209 AC: 52421 AN: 250440 AF XY: 0.210

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.218 AC: 318153 AN: 1460694 Hom.: 35348 Cov.: 32 AF XY: 0.219 AC XY: 158796 AN XY: 726664

African (AFR) AF: 0.238 AC: 7972 AN: 33440

American (AMR) AF: 0.167 AC: 7446 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5202 AN: 26118

East Asian (EAS) AF: 0.178 AC: 7048 AN: 39698

South Asian (SAS) AF: 0.229 AC: 19735 AN: 86172

European-Finnish (FIN) AF: 0.233 AC: 12437 AN: 53334

Middle Eastern (MID) AF: 0.220 AC: 1209 AN: 5484

European-Non Finnish (NFE) AF: 0.220 AC: 244084 AN: 1111460

Other (OTH) AF: 0.216 AC: 13020 AN: 60330

GnomAD4 genome AF: 0.220 AC: 33512 AN: 152000 Hom.: 3841 Cov.: 32 AF XY: 0.221 AC XY: 16418 AN XY: 74312

African (AFR) AF: 0.247 AC: 10253 AN: 41448

American (AMR) AF: 0.187 AC: 2852 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3472

East Asian (EAS) AF: 0.144 AC: 745 AN: 5178

South Asian (SAS) AF: 0.231 AC: 1111 AN: 4816

European-Finnish (FIN) AF: 0.221 AC: 2335 AN: 10556

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14831 AN: 67948

Other (OTH) AF: 0.215 AC: 454 AN: 2108

Alfa AF: 0.218 Hom.: 14506

Bravo AF: 0.220

TwinsUK AF: 0.217 AC: 805

ALSPAC AF: 0.214 AC: 826

ESP6500AA AF: 0.240 AC: 1058

ESP6500EA AF: 0.221 AC: 1899

ExAC AF: 0.213 AC: 25868

Asia WGS AF: 0.195 AC: 677 AN: 3478

EpiCase AF: 0.209

EpiControl AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.3	N
PhyloP100		0.75
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.041
MutPred		0.26		Gain of catalytic residue at L129 (P = 0.0456)
MPC		0.035
ClinPred		0.010	T
GERP RS		4.8
Varity_R		0.074
gMVP		0.29
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3793706; hg19: chr10-102269085; COSMIC: COSV100944804; COSMIC: COSV100944804;