chr17-76083670-C-G

Variant names:

• chr17-76083670-C-G
• rs528551097
• NM_001013839.4:c.2033G>C

Variant summary

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

The NM_001013839.4(EXOC7):​c.2033G>C​(p.Arg678Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EXOC7 NM_001013839.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC7	NM_001013839.4	c.2033G>C	p.Arg678Pro	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.2033G>C	p.Arg678Pro	missense_variant	Exon 19 of 19	1	NM_001013839.4	ENSP00000468404.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251176 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461556 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727052

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	.;.;T;T;T;T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D;D;.;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	.;.;M;.;.;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.3	D;.;D;.;.;.;.;D
REVEL	Benign	0.22
Sift	Uncertain	0.010	D;.;D;.;.;.;.;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;D;D;D
Polyphen		0.92	P;P;D;P;P;.;P;P
Vest4		0.47
MutPred		0.71		.;.;Gain of glycosylation at S734 (P = 0.0477);.;.;.;.;.;
MVP		0.65
MPC		1.3
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.65
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs528551097; hg19: chr17-74079751;