NM_015238.3:c.1185-3222C>T

Variant names:

• chr5-168418786-C-T
• rs17070145
• NM_015238.3:c.1185-3222C>T

Variant summary

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

The NM_015238.3(WWC1):​c.1185-3222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,876 control chromosomes in the GnomAD database, including 15,691 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.43 (15691 hom., cov: 31)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.343
• Publications: 119 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015238.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWC1	NM_015238.3	MANE Select	c.1185-3222C>T		intron	N/A	NP_056053.1
	WWC1	NM_001161661.2		c.1185-3222C>T		intron	N/A	NP_001155133.1
	WWC1	NM_001161662.2		c.1185-3222C>T		intron	N/A	NP_001155134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWC1	ENST00000265293.9	TSL:1 MANE Select	c.1185-3222C>T		intron	N/A	ENSP00000265293.4
	WWC1	ENST00000393895.7	TSL:1	c.1068-3222C>T		intron	N/A	ENSP00000377473.3
	WWC1	ENST00000524228.5	TSL:1	c.513-3222C>T		intron	N/A	ENSP00000429339.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65656 AN: 151758 Hom.: 15641 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.433 AC: 65773 AN: 151876 Hom.: 15691 Cov.: 31 AF XY: 0.436 AC XY: 32379 AN XY: 74212

African (AFR) AF: 0.585 AC: 24213 AN: 41412

American (AMR) AF: 0.500 AC: 7638 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1145 AN: 3462

East Asian (EAS) AF: 0.770 AC: 3932 AN: 5108

South Asian (SAS) AF: 0.300 AC: 1436 AN: 4790

European-Finnish (FIN) AF: 0.419 AC: 4432 AN: 10570

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21591 AN: 67952

Other (OTH) AF: 0.399 AC: 840 AN: 2106

Alfa AF: 0.389 Hom.: 6416

Bravo AF: 0.455

Asia WGS AF: 0.523 AC: 1817 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Memory quantitative trait locus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.60
PhyloP100		0.34
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: rs17070145; hg19: chr5-167845791; COSMIC: COSV54648238; COSMIC: COSV54648238;