Variant 4-82827405-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001077207.4(SEC31A):c.3255A>C(p.Glu1085Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SEC31A
NM_001077207.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.524

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40337107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC31A	NM_001077207.4 linkuse as main transcript	c.3255A>C	p.Glu1085Asp	missense_variant	24/27	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.3255A>C	p.Glu1085Asp	missense_variant	24/27	1	NM_001077207.4	ENSP00000378721.2		O94979-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251236

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

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

Jul 25, 2023

The c.3255A>C (p.E1085D) alteration is located in exon 24 (coding exon 23) of the SEC31A gene. This alteration results from a A to C substitution at nucleotide position 3255, causing the glutamic acid (E) at amino acid position 1085 to be replaced by an aspartic acid (D). 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

0.27

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

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

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

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

M_CAP

Benign

0.029

MetaRNN

Benign

0.40

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

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.5

.;.;M;.;.;.;M;.;.;.;M;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

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

REVEL

Benign

0.18

Sift

Benign

0.042

D;T;T;T;T;T;T;T;T;T;T;D;T

Sift4G

Benign

0.46

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

Polyphen

1.0

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

Vest4

0.69

MutPred

0.12

.;.;Loss of glycosylation at S1080 (P = 0.0401);.;.;.;Loss of glycosylation at S1080 (P = 0.0401);.;.;.;Loss of glycosylation at S1080 (P = 0.0401);.;.;

MVP

0.31

MPC

0.63

ClinPred

0.67

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.21

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