10-28533924-G-A

Position:

• chr10-28533924-G-A

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.42-74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,559,918 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0091 (8 hom., cov: 32)
  • Exomes 𝑓: 0.013 (167 hom.)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.185

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=-0.89).
• BP6: Variant 10-28533924-G-A is Benign according to our data. Variant chr10-28533924-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1197674.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1391 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WAC	NM_016628.5	c.42-74G>A		intron_variant		ENST00000354911.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WAC	ENST00000354911.9	c.42-74G>A		intron_variant		1	NM_016628.5	P3

Frequencies

GnomAD3 genomes AF: 0.00915 AC: 1392 AN: 152166 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.0127 AC: 17879 AN: 1407642 Hom.: 167 Cov.: 25 AF XY: 0.0124 AC XY: 8734 AN XY: 702208

Gnomad4 AFR exome AF: 0.00257

Gnomad4 AMR exome AF: 0.00754

Gnomad4 ASJ exome AF: 0.0184

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00553

Gnomad4 FIN exome AF: 0.00289

Gnomad4 NFE exome AF: 0.0146

Gnomad4 OTH exome AF: 0.0127

GnomAD4 genome AF: 0.00913 AC: 1391 AN: 152276 Hom.: 8 Cov.: 32 AF XY: 0.00881 AC XY: 656 AN XY: 74466

Gnomad4 AFR AF: 0.00298

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.0145

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00617 Hom.: 3

Bravo AF: 0.00992

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

GeneDx

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs182451824; hg19: chr10-28822853;