Variant 10-100488056-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015490.4(SEC31B):c.3331T>C(p.Tyr1111His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 1,613,810 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 15 hom. )

Consequence

SEC31B
NM_015490.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0230

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008942723).

BP6

Variant 10-100488056-A-G is Benign according to our data. Variant chr10-100488056-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2640757.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC31B	NM_015490.4 linkuse as main transcript	c.3331T>C	p.Tyr1111His	missense_variant	25/26	ENST00000370345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC31B	ENST00000370345.8 linkuse as main transcript	c.3331T>C	p.Tyr1111His	missense_variant	25/26	1	NM_015490.4	P1	Q9NQW1-1

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

407

AN:

151856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000678

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00331

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00459

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.00261

AC:

657

AN:

251424

Hom.:

AF XY:

0.00274

AC XY:

373

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.00416

Gnomad NFE exome

AF:

0.00392

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00308

AC:

4504

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2255

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00225

Gnomad4 FIN exome

AF:

0.00444

Gnomad4 NFE exome

AF:

0.00349

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

151974

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

181

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.000676

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00331

Gnomad4 NFE

AF:

0.00459

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.00352

Hom.:

Bravo

AF:

0.00212

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00264

AC:

321

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00420

EpiControl

AF:

0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SEC31B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.7

DANN

Benign

0.87

DEOGEN2

Benign

0.015

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.22

M_CAP

Benign

0.0049

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

REVEL

Benign

0.045

Sift

Benign

0.52

Sift4G

Benign

0.55

Polyphen

0.0010

Vest4

0.16

MVP

0.076

MPC

0.039

ClinPred

0.0026

GERP RS

-2.0

Varity_R

0.026

gMVP

0.15

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over