10-28533812-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.42-186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 989,418 control chromosomes in the GnomAD database, including 103 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 (95 hom.)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0430

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=-0.91).
• BP6: Variant 10-28533812-C-T is Benign according to our data. Variant chr10-28533812-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1199167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1391 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WAC	NM_016628.5	c.42-186C>T		intron_variant		ENST00000354911.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WAC	ENST00000354911.9	c.42-186C>T		intron_variant		1	NM_016628.5	P3

Frequencies

GnomAD3 genomes AF: 0.00916 AC: 1391 AN: 151886 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.00671

GnomAD4 exome AF: 0.0125 AC: 10506 AN: 837428 Hom.: 95 Cov.: 11 AF XY: 0.0123 AC XY: 5205 AN XY: 423828

Gnomad4 AFR exome AF: 0.00262

Gnomad4 AMR exome AF: 0.00879

Gnomad4 ASJ exome AF: 0.0188

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00544

Gnomad4 FIN exome AF: 0.00292

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.0127

GnomAD4 genome AF: 0.00915 AC: 1390 AN: 151990 Hom.: 8 Cov.: 32 AF XY: 0.00879 AC XY: 653 AN XY: 74282

Gnomad4 AFR AF: 0.00299

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00208

Gnomad4 NFE AF: 0.0145

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00927 Hom.: 7

Bravo AF: 0.00992

Asia WGS AF: 0.00202 AC: 7 AN: 3470

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	-0.91
Cadd	Benign	8.0
Dann	Benign	0.82
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4

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: rs148938334; hg19: chr10-28822741;