Variant 9-136447239-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014866.2(SEC16A):c.6685G>A(p.Val2229Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,442,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SEC16A
NM_014866.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

SEC16A (HGNC:29006): (SEC16 homolog A, endoplasmic reticulum export factor) This gene encodes a protein that forms part of the Sec16 complex. This protein has a role in protein transport from the endoplasmic reticulum (ER) to the Golgi and mediates COPII vesicle formation at the transitional ER. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Feb 2013]

SEC16A links:

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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=0.104625106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC16A	NM_014866.2 link	c.6685G>A	p.Val2229Met	missense_variant	27/32	ENST00000684901.1	NP_055681.1	O15027-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC16A	ENST00000684901.1 link	c.6685G>A	p.Val2229Met	missense_variant	27/32		NM_014866.2	ENSP00000508822.1		O15027-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000277

AC:

AN:

216918

Hom.:

AF XY:

0.0000339

AC XY:

AN XY:

117824

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:

0.000149

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000205

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1442638

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

715756

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.000229

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000453

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

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

Sep 04, 2024

The c.6685G>A (p.V2229M) alteration is located in exon 27 (coding exon 25) of the SEC16A gene. This alteration results from a G to A substitution at nucleotide position 6685, causing the valine (V) at amino acid position 2229 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

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

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.92

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

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.10

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

MetaSVM

Benign

-0.84

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.93

N;.;N;N;N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0060

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

Sift4G

Benign

0.13

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

Polyphen

1.0, 1.0

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

Vest4

0.21

MutPred

0.17

.;.;.;.;Loss of phosphorylation at T2053 (P = 0.081);.;Loss of phosphorylation at T2053 (P = 0.081);

MVP

0.29

MPC

0.30

ClinPred

0.25

GERP RS

2.2

Varity_R

0.069

gMVP

0.37

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