dbSNP rs3793706: SEC31B:p.Leu129Phe (chr10-100509328-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.22 ( 3841 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35348 hom. )

Consequence

SEC31B
NM_015490.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.753

Variant links:

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]

SEC31B links:

ENSG00000255339 (HGNC:):

ENSG00000255339 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC31B	NM_015490.4 link	c.387G>T	p.Leu129Phe	missense_variant	Exon 4 of 26	ENST00000370345.8	NP_056305.1	Q9NQW1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC31B	ENST00000370345.8 link	c.387G>T	p.Leu129Phe	missense_variant	Exon 4 of 26	1	NM_015490.4	ENSP00000359370.3		Q9NQW1-1
ENSG00000255339	ENST00000557395.5 link	n.*324-226G>T		intron_variant	Intron 7 of 9	2		ENSP00000456832.1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33487

AN:

151882

Hom.:

3830

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.209

AC:

52421

AN:

250440

Hom.:

5754

AF XY:

0.210

AC XY:

28487

AN XY:

135406

show subpopulations

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 SAS exome

AF:

0.225

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.:

AF XY:

0.219

AC XY:

158796

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.167

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:

0.220

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.220

AC:

33512

AN:

152000

Hom.:

3841

Cov.:

AF XY:

0.221

AC XY:

16418

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.247

Gnomad4 AMR

AF:

0.187

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.215

Alfa

AF:

0.217

Hom.:

9538

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.026

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.3

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.6

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.041

MutPred

0.26

Gain of catalytic residue at L129 (P = 0.0456);

MPC

0.035

ClinPred

0.010

GERP RS

4.8

Varity_R

0.074

gMVP

0.29

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over