chr9-136446907-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014866.2(SEC16A):​c.6740G>A​(p.Gly2247Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000961 in 1,613,458 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 0.000099 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000096 ( 1 hom. )

Consequence

SEC16A
NM_014866.2 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.019035041).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC16ANM_014866.2 linkuse as main transcriptc.6740G>A p.Gly2247Glu missense_variant 28/32 ENST00000684901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC16AENST00000684901.1 linkuse as main transcriptc.6740G>A p.Gly2247Glu missense_variant 28/32 NM_014866.2 A2O15027-1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152140
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00173
Gnomad SAS
AF:
0.000830
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000885
AC:
22
AN:
248622
Hom.:
0
AF XY:
0.000111
AC XY:
15
AN XY:
134940
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000780
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000958
AC:
140
AN:
1461200
Hom.:
1
Cov.:
32
AF XY:
0.0000880
AC XY:
64
AN XY:
726888
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00242
Gnomad4 SAS exome
AF:
0.000278
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152258
Hom.:
1
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00174
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.000124
AC:
15
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

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 submitterclinical testingAmbry GeneticsNov 17, 2023The c.6740G>A (p.G2247E) alteration is located in exon 28 (coding exon 26) of the SEC16A gene. This alteration results from a G to A substitution at nucleotide position 6740, causing the glycine (G) at amino acid position 2247 to be replaced by a glutamic acid (E). 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
-0.33
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
.;T;T;T;.;T;.
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.70
T;T;T;T;T;T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.019
T;T;T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.7
N;.;N;N;N;D;N
REVEL
Benign
0.12
Sift
Uncertain
0.0060
D;.;D;T;T;D;D
Sift4G
Benign
0.49
T;T;T;T;T;T;T
Polyphen
0.24, 0.99
.;B;.;.;.;D;.
Vest4
0.25
MutPred
0.23
.;.;.;.;Gain of helix (P = 0.0496);.;Gain of helix (P = 0.0496);
MVP
0.20
MPC
0.45
ClinPred
0.12
T
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.15

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.

Other links and lift over

dbSNP: rs546048494; hg19: chr9-139341359; COSMIC: COSV51523313; COSMIC: COSV51523313; API