5-168408534-C-T

Variant names:

• chr5-168408534-C-T
• rs17551608
• NM_015238.3:c.748C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015238.3(WWC1):​c.748C>T​(p.Arg250Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,613,978 control chromosomes in the GnomAD database, including 18,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1187 hom., cov: 31)
  • Exomes 𝑓: 0.15 (16959 hom.)
• Consequence: WWC1 NM_015238.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34
• Publications: 27 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019046664).
• BP6: Variant 5-168408534-C-T is Benign according to our data. Variant chr5-168408534-C-T is described in ClinVar as Benign. ClinVar VariationId is 1245599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWC1	NM_015238.3	MANE Select	c.748C>T	p.Arg250Cys	missense	Exon 7 of 23	NP_056053.1	Q8IX03-1
	WWC1	NM_001161661.2		c.748C>T	p.Arg250Cys	missense	Exon 7 of 23	NP_001155133.1	Q8IX03-2
	WWC1	NM_001161662.2		c.748C>T	p.Arg250Cys	missense	Exon 7 of 23	NP_001155134.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWC1	ENST00000265293.9	TSL:1 MANE Select	c.748C>T	p.Arg250Cys	missense	Exon 7 of 23	ENSP00000265293.4	Q8IX03-1
	WWC1	ENST00000393895.7	TSL:1	c.631C>T	p.Arg211Cys	missense	Exon 6 of 22	ENSP00000377473.3	H3BLZ3
	WWC1	ENST00000524228.5	TSL:1	c.76C>T	p.Arg26Cys	missense	Exon 2 of 18	ENSP00000429339.1	H0YBE8

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17312 AN: 152088 Hom.: 1187 Cov.: 31

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.122 AC: 30545 AN: 251194 AF XY: 0.126

Gnomad AFR exome AF: 0.0415

Gnomad AMR exome AF: 0.0801

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.00435

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.147 AC: 214333 AN: 1461772 Hom.: 16959 Cov.: 32 AF XY: 0.146 AC XY: 106332 AN XY: 727186

African (AFR) AF: 0.0384 AC: 1285 AN: 33478

American (AMR) AF: 0.0831 AC: 3716 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3213 AN: 26134

East Asian (EAS) AF: 0.00378 AC: 150 AN: 39696

South Asian (SAS) AF: 0.114 AC: 9843 AN: 86218

European-Finnish (FIN) AF: 0.162 AC: 8642 AN: 53414

Middle Eastern (MID) AF: 0.114 AC: 657 AN: 5768

European-Non Finnish (NFE) AF: 0.160 AC: 178413 AN: 1111946

Other (OTH) AF: 0.139 AC: 8414 AN: 60394

GnomAD4 genome AF: 0.114 AC: 17312 AN: 152206 Hom.: 1187 Cov.: 31 AF XY: 0.113 AC XY: 8408 AN XY: 74410

African (AFR) AF: 0.0432 AC: 1795 AN: 41540

American (AMR) AF: 0.103 AC: 1567 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5188

South Asian (SAS) AF: 0.111 AC: 534 AN: 4810

European-Finnish (FIN) AF: 0.174 AC: 1847 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10719 AN: 68014

Other (OTH) AF: 0.119 AC: 251 AN: 2110

Alfa AF: 0.139 Hom.: 7918

Bravo AF: 0.104

TwinsUK AF: 0.170 AC: 629

ALSPAC AF: 0.160 AC: 617

ESP6500AA AF: 0.0443 AC: 195

ESP6500EA AF: 0.156 AC: 1339

ExAC AF: 0.121 AC: 14713

Asia WGS AF: 0.0550 AC: 192 AN: 3478

EpiCase AF: 0.163

EpiControl AF: 0.155

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
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.038
Eigen_PC	Benign	-0.034
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.3
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.11
Sift	Uncertain	0.017	D
Sift4G	Benign	0.099	T
Polyphen		0.94	P
Vest4		0.083
MPC		0.38
ClinPred		0.013	T
GERP RS		4.3
Varity_R		0.088
gMVP		0.17
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17551608; hg19: chr5-167835539; COSMIC: COSV54652036; COSMIC: COSV54652036;