chr1-231335522-AT-A

Position:

• chr1-231335522-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_175876.5(EXOC8):​c.*45del 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC8	NM_175876.5	c.*45del		3_prime_UTR_variant	1/1	ENST00000366645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC8	ENST00000366645.1	c.*45del		3_prime_UTR_variant	1/1		NM_175876.5	P1

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

GnomAD3 exomes AF: 0.211 AC: 32999 AN: 156668 Hom.: 4426 AF XY: 0.204 AC XY: 17214 AN XY: 84410

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 SAS exome AF: 0.201

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

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.213

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

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.229

Alfa AF: 0.0996 Hom.: 156

Bravo AF: 0.250

Asia WGS AF: 0.236 AC: 822 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

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