rs10483681

Positions:

• chr14-57231956-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006544.4(EXOC5):​c.939-241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 367,824 control chromosomes in the GnomAD database, including 15,874 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8074 hom., cov: 31)
  • Exomes 𝑓: 0.26 (7800 hom.)
• Consequence: EXOC5 NM_006544.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

Genes affected

EXOC5 (HGNC:10696): (exocyst complex component 5) The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. The complex is also essential for the biogenesis of epithelial cell surface polarity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC5	NM_006544.4	c.939-241A>G		intron_variant		ENST00000621441.5	NP_006535.1
EXOC5	XM_005267272.4	c.1053-241A>G		intron_variant			XP_005267329.1
EXOC5	XM_047430882.1	c.774-241A>G		intron_variant			XP_047286838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC5	ENST00000621441.5	c.939-241A>G		intron_variant		1	NM_006544.4	ENSP00000484855	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47021 AN: 151866 Hom.: 8063 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.260 AC: 56214 AN: 215840 Hom.: 7800 Cov.: 2 AF XY: 0.260 AC XY: 29495 AN XY: 113404

Gnomad4 AFR exome AF: 0.469

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.310 AC: 47060 AN: 151984 Hom.: 8074 Cov.: 31 AF XY: 0.302 AC XY: 22428 AN XY: 74296

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.298

Alfa AF: 0.282 Hom.: 3406

Bravo AF: 0.314

Asia WGS AF: 0.186 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.65

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: rs10483681; hg19: chr14-57698674;