rs332148

Variant names:

• chr10-28582316-A-T
• rs332148
• NM_016628.5:c.275-1083A>T

Variant summary

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

The NM_016628.5(WAC):​c.275-1083A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,248 control chromosomes in the GnomAD database, including 1,476 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 0.12 (1476 hom., cov: 32)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679
• Publications: 6 publications found

Genes affected

WAC (HGNC:17327): (WW domain containing adaptor with coiled-coil) The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its exact function is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

WAC Gene-Disease associations (from GenCC):

• DeSanto-Shinawi syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• DeSanto-Shinawi syndrome due to WAC point mutation

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAC	NM_016628.5	c.275-1083A>T		intron_variant	Intron 3 of 13	ENST00000354911.9	NP_057712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WAC	ENST00000354911.9	c.275-1083A>T		intron_variant	Intron 3 of 13	1	NM_016628.5	ENSP00000346986.4
WAC	ENST00000428935.6	c.140-1083A>T		intron_variant	Intron 3 of 7	2		ENSP00000399706.3
WAC	ENST00000651885.1	c.293-1083A>T		intron_variant	Intron 3 of 4			ENSP00000498678.1
WAC	ENST00000651598.1	c.140-1083A>T		intron_variant	Intron 3 of 5			ENSP00000498480.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18303 AN: 152130 Hom.: 1476 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.120 AC: 18299 AN: 152248 Hom.: 1476 Cov.: 32 AF XY: 0.118 AC XY: 8821 AN XY: 74450

African (AFR) AF: 0.0344 AC: 1430 AN: 41546

American (AMR) AF: 0.119 AC: 1819 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5188

South Asian (SAS) AF: 0.118 AC: 570 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1247 AN: 10604

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12322 AN: 68004

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.145 Hom.: 227

Bravo AF: 0.116

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.44
PhyloP100		0.68
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: rs332148; hg19: chr10-28871245;