rs35468792

Variant names:

• chr1-231335522-AT-A
• rs35468792
• NM_175876.5:c.*45delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_175876.5(EXOC8):​c.*45delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,429,290 control chromosomes in the GnomAD database, including 34,369 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4525 hom., cov: 24)
  • Exomes 𝑓: 0.21 (29844 hom.)
• Consequence: EXOC8 NM_175876.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.397
• Publications: 4 publications found

Genes affected

EXOC8 (HGNC:24659): (exocyst complex component 8) This gene encodes a component of the exocyst complex, an evolutionarily conserved multi-protein complex that plays a critical role in vesicular trafficking and the secretory pathway by targeting post-Golgi vesicles to the plasma membrane. This protein is a target of activated Ral subfamily of GTPases and thereby regulates exocytosis by tethering vesicles to the plasma membrane. Mutations in this gene may be related to Joubert syndrome. [provided by RefSeq, Sep 2016]

EXOC8 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, seizures, and brain atrophy

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-231335522-AT-A is Benign according to our data. Variant chr1-231335522-AT-A is described in ClinVar as Benign. ClinVar VariationId is 1257331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175876.5. 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
	EXOC8	NM_175876.5	MANE Select	c.*45delA		3_prime_UTR	Exon 1 of 1	NP_787072.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC8	ENST00000366645.1	TSL:6 MANE Select	c.*45delA		3_prime_UTR	Exon 1 of 1	ENSP00000355605.2	Q8IYI6

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36301 AN: 151840 Hom.: 4520 Cov.: 24

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.227

GnomAD2 exomes AF: 0.211 AC: 32999 AN: 156668 AF XY: 0.204

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.348

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.232

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.212 AC: 270722 AN: 1277332 Hom.: 29844 Cov.: 15 AF XY: 0.212 AC XY: 132511 AN XY: 624148

African (AFR) AF: 0.306 AC: 8859 AN: 28912

American (AMR) AF: 0.342 AC: 8078 AN: 23628

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 4207 AN: 18494

East Asian (EAS) AF: 0.250 AC: 9308 AN: 37194

South Asian (SAS) AF: 0.246 AC: 12442 AN: 50476

European-Finnish (FIN) AF: 0.188 AC: 8477 AN: 45210

Middle Eastern (MID) AF: 0.180 AC: 687 AN: 3808

European-Non Finnish (NFE) AF: 0.204 AC: 207577 AN: 1017566

Other (OTH) AF: 0.213 AC: 11087 AN: 52044

GnomAD4 genome AF: 0.239 AC: 36337 AN: 151958 Hom.: 4525 Cov.: 24 AF XY: 0.239 AC XY: 17760 AN XY: 74254

African (AFR) AF: 0.305 AC: 12621 AN: 41418

American (AMR) AF: 0.281 AC: 4294 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1325 AN: 5158

South Asian (SAS) AF: 0.239 AC: 1153 AN: 4818

European-Finnish (FIN) AF: 0.180 AC: 1901 AN: 10532

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13573 AN: 67982

Other (OTH) AF: 0.229 AC: 484 AN: 2112

Alfa AF: 0.0996 Hom.: 156

Bravo AF: 0.250

Asia WGS AF: 0.236 AC: 822 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35468792; hg19: chr1-231471268; COSMIC: COSV50477542; COSMIC: COSV50477542;