Variant 10-100489284-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015490.4(SEC31B):c.3139C>A(p.Pro1047Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000822 in 1,459,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SEC31B
NM_015490.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC31B	NM_015490.4 linkuse as main transcript	c.3139C>A	p.Pro1047Thr	missense_variant	23/26	ENST00000370345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC31B	ENST00000370345.8 linkuse as main transcript	c.3139C>A	p.Pro1047Thr	missense_variant	23/26	1	NM_015490.4	P1	Q9NQW1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248116

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1459854

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2022

The c.3139C>A (p.P1047T) alteration is located in exon 23 (coding exon 22) of the SEC31B gene. This alteration results from a C to A substitution at nucleotide position 3139, causing the proline (P) at amino acid position 1047 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.76

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.14

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.52

MutPred

0.25

Gain of glycosylation at P1047 (P = 0.018);

MVP

0.59

MPC

0.050

ClinPred

0.94

GERP RS

4.7

Varity_R

0.21

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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