Variant 9-136447595-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014866.2(SEC16A):c.6533C>T(p.Pro2178Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000957 in 1,613,782 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 2 hom. )

Consequence

SEC16A
NM_014866.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.71

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:

SEC16A (HGNC:):

SEC16A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05121559).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC16A	NM_014866.2 linkuse as main transcript	c.6533C>T	p.Pro2178Leu	missense_variant	26/32	ENST00000684901.1	NP_055681.1	O15027-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC16A	ENST00000684901.1 linkuse as main transcript	c.6533C>T	p.Pro2178Leu	missense_variant	26/32		NM_014866.2	ENSP00000508822.1		O15027-1

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000450

AC:

112

AN:

248654

Hom.:

AF XY:

0.000511

AC XY:

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.000259

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000880

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000991

AC:

1449

AN:

1461438

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

669

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.000630

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000919

Hom.:

Bravo

AF:

0.000688

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000516

AC:

ESP6500EA

AF:

0.00109

AC:

ExAC

AF:

0.000438

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000889

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 14, 2021

The c.6533C>T (p.P2178L) alteration is located in exon 26 (coding exon 24) of the SEC16A gene. This alteration results from a C to T substitution at nucleotide position 6533, causing the proline (P) at amino acid position 2178 to be replaced by a leucine (L). 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

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.10

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

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

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

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.051

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

MetaSVM

Benign

-0.82

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

N;.;D;D;N;D;N

REVEL

Benign

0.15

Sift

Uncertain

0.017

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

Sift4G

Uncertain

0.0070

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

Polyphen

0.90, 0.63

.;P;.;.;.;P;.

Vest4

0.35

MVP

0.25

MPC

0.078

ClinPred

0.056

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.17

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