10-28533630-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016628.5(WAC):c.41+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,582,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000063 (1 hom.)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.144

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-28533630-C-T is Benign according to our data. Variant chr10-28533630-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 746016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WAC	NM_016628.5	c.41+10C>T		intron_variant		ENST00000354911.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WAC	ENST00000354911.9	c.41+10C>T		intron_variant		1	NM_016628.5	P3

Frequencies

GnomAD3 genomes AF: 0.0000809 AC: 12 AN: 148318 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000741

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000220

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000119

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000929 AC: 22 AN: 236830 Hom.: 0 AF XY: 0.0000844 AC XY: 11 AN XY: 130356

Gnomad AFR exome AF: 0.0000716

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000814

Gnomad SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.0000285

Gnomad OTH exome AF: 0.000346

GnomAD4 exome AF: 0.0000635 AC: 91 AN: 1433692 Hom.: 1 Cov.: 32 AF XY: 0.0000631 AC XY: 45 AN XY: 713334

Gnomad4 AFR exome AF: 0.0000315

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00162

Gnomad4 SAS exome AF: 0.0000352

Gnomad4 FIN exome AF: 0.0000602

Gnomad4 NFE exome AF: 0.0000182

Gnomad4 OTH exome AF: 0.0000511

GnomAD4 genome AF: 0.0000808 AC: 12 AN: 148450 Hom.: 0 Cov.: 32 AF XY: 0.0000414 AC XY: 3 AN XY: 72434

Gnomad4 AFR AF: 0.0000739

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000221

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000119

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000145 Hom.: 0

Asia WGS AF: 0.000318 AC: 1 AN: 3164

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	16
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs199699143; hg19: chr10-28822559;