Variant 4-82842240-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001077207.4(SEC31A):c.2868C>T(p.Gly956Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,613,682 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 16 hom., cov: 31)

Exomes 𝑓: 0.0051 ( 71 hom. )

Consequence

SEC31A
NM_001077207.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

SEC31A (HGNC:17052): (SEC31 homolog A, COPII coat complex component) The protein encoded by this gene shares similarity with the yeast Sec31 protein, and is a component of the outer layer of the coat protein complex II (COPII). The encoded protein is involved in vesicle budding from the endoplasmic reticulum (ER) and contains multiple WD repeats near the N-terminus and a proline-rich region in the C-terminal half. It associates with the protein encoded by the SEC13 homolog, nuclear pore and COPII coat complex component (SEC13), and is required for ER-Golgi transport. Monoubiquitylation of this protein by CUL3-KLHL12 was found to regulate the size of COPII coats to accommodate unusually shaped cargo. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SEC31A links:

SEC31A (HGNC:):

SEC31A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 4-82842240-G-A is Benign according to our data. Variant chr4-82842240-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654848.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.55 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC31A	NM_001077207.4 linkuse as main transcript	c.2868C>T	p.Gly956Gly	synonymous_variant	22/27	ENST00000395310.7	NP_001070675.1	O94979-1A1LU61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC31A	ENST00000395310.7 linkuse as main transcript	c.2868C>T	p.Gly956Gly	synonymous_variant	22/27	1	NM_001077207.4	ENSP00000378721.2		O94979-1

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

988

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00664

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00582

Gnomad FIN

AF:

0.0484

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00495

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00773

AC:

1937

AN:

250520

Hom.:

AF XY:

0.00786

AC XY:

1064

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00520

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00514

Gnomad FIN exome

AF:

0.0479

Gnomad NFE exome

AF:

0.00512

Gnomad OTH exome

AF:

0.00671

GnomAD4 exome

AF:

0.00511

AC:

7469

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00517

AC XY:

3761

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.00514

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00478

Gnomad4 FIN exome

AF:

0.0446

Gnomad4 NFE exome

AF:

0.00364

Gnomad4 OTH exome

AF:

0.00588

GnomAD4 genome

AF:

0.00649

AC:

988

AN:

152240

Hom.:

Cov.:

AF XY:

0.00834

AC XY:

621

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00664

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00582

Gnomad4 FIN

AF:

0.0484

Gnomad4 NFE

AF:

0.00495

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00249

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00436

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

Nov 01, 2023

SEC31A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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