chr9-136441762-A-G

Position:

• chr9-136441762-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014866.2(SEC16A):​c.7067T>C​(p.Leu2356Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEC16A NM_014866.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC16A	NM_014866.2	c.7067T>C	p.Leu2356Pro	missense_variant	32/32	ENST00000684901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC16A	ENST00000684901.1	c.7067T>C	p.Leu2356Pro	missense_variant	32/32		NM_014866.2	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Apr 11, 2023

The c.7067T>C (p.L2356P) alteration is located in exon 32 (coding exon 30) of the SEC16A gene. This alteration results from a T to C substitution at nucleotide position 7067, causing the leucine (L) at amino acid position 2356 to be replaced by a proline (P). 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	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	.;T;T;T;.;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.46	T;T;T;T;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D
MetaSVM	Benign	-0.49	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	N;.;N;N;N;N;N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;.;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0	.;D;.;.;.;D;.
Vest4		0.63
MVP		0.39
MPC		0.50
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.24
gMVP		0.67

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: chr9-139336214;