chr17-76083694-T-C

Variant names:

• chr17-76083694-T-C
• NM_001013839.4:c.2009A>G

Variant summary

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

The NM_001013839.4(EXOC7):​c.2009A>G​(p.Glu670Gly) variant causes a missense change. 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: EXOC7 NM_001013839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91

Genes affected

EXOC7 (HGNC:23214): (exocyst complex component 7) The protein encoded by this gene is a component of the exocyst complex. The exocyst complex plays a critical role in vesicular trafficking and the secretory pathway by targeting post-Golgi vesicles to the plasma membrane. The encoded protein is required for assembly of the exocyst complex and docking of the complex to the plasma membrane. The encoded protein may also play a role in pre-mRNA splicing through interactions with pre-mRNA-processing factor 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Nov 2011]

ZACN (HGNC:29504): (zinc activated ion channel) LGICZ1 is a zinc-activated ligand-gated ion channel that defines a new subgroup of the cysteine-loop superfamily of ligand-gated ion channels (Davies et al., 2003 [PubMed 12381728]).[supplied by OMIM, Mar 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=0.36424482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC7	NM_001013839.4	c.2009A>G	p.Glu670Gly	missense_variant	Exon 19 of 19	ENST00000589210.6	NP_001013861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC7	ENST00000589210.6	c.2009A>G	p.Glu670Gly	missense_variant	Exon 19 of 19	1	NM_001013839.4	ENSP00000468404.1

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

Inborn genetic diseases Uncertain:1

Dec 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2162A>G (p.E721G) alteration is located in exon 20 (coding exon 20) of the EXOC7 gene. This alteration results from a A to G substitution at nucleotide position 2162, causing the glutamic acid (E) at amino acid position 721 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	.;.;T;T;T;T;.;.
Eigen	Benign	0.087
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;.;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.36	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.7	.;.;M;.;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.5	D;.;D;.;.;.;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.019	D;.;D;.;.;.;.;D
Sift4G	Uncertain	0.012	D;D;D;D;D;D;D;D
Polyphen		0.076	B;B;B;B;B;.;B;B
Vest4		0.18
MutPred		0.75		.;.;Gain of sheet (P = 0.0827);.;.;.;.;.;
MVP		0.69
MPC		0.52
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.30
gMVP		0.42

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: chr17-74079775;