chr5-168407805-T-C

Variant names:

• chr5-168407805-T-C
• rs17633196
• NM_015238.3:c.721-702T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015238.3(WWC1):​c.721-702T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,092 control chromosomes in the GnomAD database, including 1,582 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 0.14 (1582 hom., cov: 31)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 0 publications found

Genes affected

WWC1 (HGNC:29435): (WW and C2 domain containing 1) The protein encoded by this gene is a cytoplasmic phosphoprotein that interacts with PRKC-zeta and dynein light chain-1. Alleles of this gene have been found that enhance memory in some individuals. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC1	NM_015238.3	c.721-702T>C		intron_variant	Intron 6 of 22	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.721-702T>C		intron_variant	Intron 6 of 22	1	NM_015238.3	ENSP00000265293.4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21082 AN: 151974 Hom.: 1581 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.138

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.139 AC: 21109 AN: 152092 Hom.: 1582 Cov.: 31 AF XY: 0.137 AC XY: 10210 AN XY: 74340

African (AFR) AF: 0.173 AC: 7180 AN: 41478

American (AMR) AF: 0.106 AC: 1613 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3466

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5178

South Asian (SAS) AF: 0.113 AC: 543 AN: 4814

European-Finnish (FIN) AF: 0.163 AC: 1725 AN: 10578

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9212 AN: 67996

Other (OTH) AF: 0.136 AC: 288 AN: 2114

Alfa AF: 0.137 Hom.: 1407

Bravo AF: 0.136

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.65
DANN	Benign	0.38
PhyloP100		-2.0
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: rs17633196; hg19: chr5-167834810;