chr4-82842452-C-T

Position:

chr4-82842452-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077207.4(SEC31A):c.2656G>A(p.Gly886Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,613,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

SEC31A
NM_001077207.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.57

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14470553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC31A	NM_001077207.4 linkuse as main transcript	c.2656G>A	p.Gly886Arg	missense_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.2656G>A	p.Gly886Arg	missense_variant	22/27	1	NM_001077207.4	ENSP00000378721.2		O94979-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000769

AC:

AN:

246968

Hom.:

AF XY:

0.0000748

AC XY:

AN XY:

133708

show subpopulations

Gnomad AFR exome

AF:

0.000128

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:

0.000153

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000227

AC:

331

AN:

1460884

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

169

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000293

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000145

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000132

ExAC

AF:

0.0000494

AC:

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

Aug 27, 2024

The c.2656G>A (p.G886R) alteration is located in exon 22 (coding exon 21) of the SEC31A gene. This alteration results from a G to A substitution at nucleotide position 2656, causing the glycine (G) at amino acid position 886 to be replaced by an arginine (R). 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

0.29

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.059

.;T;.;T;T;.;T;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.97

D;.;D;D;D;D;.;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.14

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.1

.;L;.;L;.;L;L;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.028

D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.11

T;T;T;T;T;T;T;T;T

Polyphen

1.0

D;D;.;D;.;D;D;.;.

Vest4

0.42

MutPred

0.37

.;Gain of solvent accessibility (P = 0.0042);.;Gain of solvent accessibility (P = 0.0042);.;Gain of solvent accessibility (P = 0.0042);Gain of solvent accessibility (P = 0.0042);.;.;

MVP

0.58

MPC

0.20

ClinPred

0.11

GERP RS

6.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.074

gMVP

0.43

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