chr17-76083670-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R678H) has been classified as Uncertain significance.

• 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
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013839.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC7	NM_001013839.4	MANE Select	c.2033G>C	p.Arg678Pro	missense	Exon 19 of 19	NP_001013861.1	Q9UPT5-1
	EXOC7	NM_001145297.4		c.2186G>C	p.Arg729Pro	missense	Exon 20 of 20	NP_001138769.1	Q9UPT5-3
	EXOC7	NM_001375976.1		c.2141G>C	p.Arg714Pro	missense	Exon 21 of 21	NP_001362905.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC7	ENST00000589210.6	TSL:1 MANE Select	c.2033G>C	p.Arg678Pro	missense	Exon 19 of 19	ENSP00000468404.1	Q9UPT5-1
	EXOC7	ENST00000335146.11	TSL:1	c.2186G>C	p.Arg729Pro	missense	Exon 20 of 20	ENSP00000334100.6	Q9UPT5-3
	EXOC7	ENST00000634349.1	TSL:1	c.2102G>C	p.Arg701Pro	missense	Exon 20 of 20	ENSP00000489266.1	Q9UPT5-6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251176 AF XY: 0.0000147

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.22
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.92	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

Other links and lift over

dbSNP: rs528551097; hg19: chr17-74079751;