3-10301302-C-T

Variant names:

• chr3-10301302-C-T
• rs199862166
• NM_183352.3:c.928G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_183352.3(SEC13):​c.928G>A​(p.Val310Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000688 in 1,614,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (1 hom.)
• Consequence: SEC13 NM_183352.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95

Genes affected

SEC13 (HGNC:10697): (SEC13 homolog, nuclear pore and COPII coat complex component) The protein encoded by this gene belongs to the SEC13 family of WD-repeat proteins. It is a constituent of the endoplasmic reticulum and the nuclear pore complex. It has similarity to the yeast SEC13 protein, which is required for vesicle biogenesis from endoplasmic reticulum during the transport of proteins. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16716045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC13	NM_183352.3	c.928G>A	p.Val310Ile	missense_variant	Exon 9 of 9	ENST00000350697.8	NP_899195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC13	ENST00000350697.8	c.928G>A	p.Val310Ile	missense_variant	Exon 9 of 9	1	NM_183352.3	ENSP00000312122.4

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.0000735

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251448 AF XY: 0.0000368

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000664 AC: 97 AN: 1461874 Hom.: 1 Cov.: 34 AF XY: 0.0000674 AC XY: 49 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000597 AC: 2 AN: 33478

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.0000756 AC: 3 AN: 39696

Gnomad4 SAS exome AF: 0.0000696 AC: 6 AN: 86258

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53412

Gnomad4 NFE exome AF: 0.0000710 AC: 79 AN: 1112010

Gnomad4 Remaining exome AF: 0.0000994 AC: 6 AN: 60392

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74308

Gnomad4 AFR AF: 0.0000241 AC: 0.0000241359 AN: 0.0000241359

Gnomad4 AMR AF: 0.000327 AC: 0.000327139 AN: 0.000327139

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000735 AC: 0.000073497 AN: 0.000073497

Gnomad4 OTH AF: 0.00144 AC: 0.00143541 AN: 0.00143541

Alfa AF: 0.0000771 Hom.: 0

Bravo AF: 0.000155

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.928G>A (p.V310I) alteration is located in exon 9 (coding exon 9) of the SEC13 gene. This alteration results from a G to A substitution at nucleotide position 928, causing the valine (V) at amino acid position 310 to be replaced by an isoleucine (I). 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	0.067
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.068	.;.;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	.;.;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.21	N;N;N;N
REVEL	Benign	0.083
Sift	Benign	0.26	T;T;T;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.026	.;.;B;.
Vest4		0.30
MVP		0.47
MPC		0.18
ClinPred		0.061	T
GERP RS		4.4
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.055
gMVP		0.23
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs199862166; hg19: chr3-10342986; COSMIC: COSV61602253; COSMIC: COSV61602253;