9-136443851-G-C

Position:

• chr9-136443851-G-C

Variant summary

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

The NM_014866.2(SEC16A):​c.6977C>G​(p.Pro2326Arg) 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: 33)
• Consequence: SEC16A NM_014866.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38995683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC16A	NM_014866.2	c.6977C>G	p.Pro2326Arg	missense_variant	31/32	ENST00000684901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC16A	ENST00000684901.1	c.6977C>G	p.Pro2326Arg	missense_variant	31/32		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

Dec 01, 2022

The c.6977C>G (p.P2326R) alteration is located in exon 31 (coding exon 29) of the SEC16A gene. This alteration results from a C to G substitution at nucleotide position 6977, causing the proline (P) at amino acid position 2326 to be replaced by an arginine (R). 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	0.18
BayesDel_addAF	Benign	-0.0023	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;T;T;T;.;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D;D
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T
MetaSVM	Benign	-0.53	T
MutationTaster	Benign	0.76	D;D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.6	D;.;D;D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;.;D;D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D;T;D
Polyphen		0.98, 0.99	.;D;.;.;.;D;.
Vest4		0.60
MVP		0.17
MPC		0.41
ClinPred		0.95	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr9-139338303;