14-39039048-T-C

Position:

• chr14-39039048-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000307712.11(SEC23A):​c.2191A>G​(p.Met731Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC23A ENST00000307712.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

Genes affected

SEC23A (HGNC:10701): (SEC23 homolog A, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family. It is part of a protein complex and found in the ribosome-free transitional face of the endoplasmic reticulum (ER) and associated vesicles. This protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The encoded protein is suggested to play a role in the ER-Golgi protein trafficking. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.337408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23A	NM_006364.4	c.2191A>G	p.Met731Val	missense_variant	19/20	ENST00000307712.11	NP_006355.2
SEC23A	XM_005267262.2	c.2263A>G	p.Met755Val	missense_variant	20/21		XP_005267319.1
SEC23A	XM_011536355.4	c.2263A>G	p.Met755Val	missense_variant	20/21		XP_011534657.1
SEC23A	XM_017020928.3	c.2191A>G	p.Met731Val	missense_variant	19/20		XP_016876417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23A	ENST00000307712.11	c.2191A>G	p.Met731Val	missense_variant	19/20	1	NM_006364.4	ENSP00000306881	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.2191A>G (p.M731V) alteration is located in exon 19 (coding exon 18) of the SEC23A gene. This alteration results from a A to G substitution at nucleotide position 2191, causing the methionine (M) at amino acid position 731 to be replaced by a valine (V). 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	0.096
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	23
DANN	Benign	0.69
DEOGEN2	Benign	0.14	.;T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.4	.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.48
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.46	T;T;T
Polyphen		0.046, 0.077	.;B;B
Vest4		0.46
MutPred		0.65		.;Gain of catalytic residue at A733 (P = 0);.;
MVP		0.84
MPC		0.49
ClinPred		0.45	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-39508252;