chr10-28569649-C-T

Variant names:

• chr10-28569649-C-T
• rs332136
• NM_016628.5:c.275-13750C>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.275-13750C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,928 control chromosomes in the GnomAD database, including 25,857 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 0.58 (25857 hom., cov: 32)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAC	NM_016628.5	c.275-13750C>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.275-13750C>T		intron_variant	Intron 3 of 13	1	NM_016628.5	ENSP00000346986.4
WAC	ENST00000428935.6	c.140-13750C>T		intron_variant	Intron 3 of 7	2		ENSP00000399706.3
WAC	ENST00000651885.1	c.293-13750C>T		intron_variant	Intron 3 of 4			ENSP00000498678.1
WAC	ENST00000651598.1	c.140-13750C>T		intron_variant	Intron 3 of 5			ENSP00000498480.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87567 AN: 151810 Hom.: 25820 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.577 AC: 87658 AN: 151928 Hom.: 25857 Cov.: 32 AF XY: 0.579 AC XY: 42944 AN XY: 74224

African (AFR) AF: 0.672 AC: 27853 AN: 41434

American (AMR) AF: 0.613 AC: 9348 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3468

East Asian (EAS) AF: 0.683 AC: 3526 AN: 5164

South Asian (SAS) AF: 0.671 AC: 3227 AN: 4810

European-Finnish (FIN) AF: 0.433 AC: 4558 AN: 10530

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.521 AC: 35382 AN: 67954

Other (OTH) AF: 0.577 AC: 1218 AN: 2110

Alfa AF: 0.564 Hom.: 4772

Bravo AF: 0.592

Asia WGS AF: 0.676 AC: 2352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.49
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs332136; hg19: chr10-28858578;