Genetic Variant WAC:c.78+19G>T (chr10-28534053-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016628.5(WAC):c.78+19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00563 in 1,573,972 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 32 hom. )

Consequence

WAC
NM_016628.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.34

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 10-28534053-G-T is Benign according to our data. Variant chr10-28534053-G-T is described in ClinVar as [Benign]. Clinvar id is 1220913.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 566 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAC	NM_016628.5 link	c.78+19G>T		intron_variant	Intron 2 of 13	ENST00000354911.9	NP_057712.2	Q9BTA9-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WAC	ENST00000354911.9 link	c.78+19G>T	intron_variant	Intron 2 of 13	1	NM_016628.5	ENSP00000346986.4	Q9BTA9-1
WAC	ENST00000428935.6 link	c.-58+19G>T	intron_variant	Intron 2 of 7	2		ENSP00000399706.3	A0A0A0MSR1
WAC	ENST00000651885.1 link	c.78+19G>T	intron_variant	Intron 2 of 4			ENSP00000498678.1	A0A494C0S5
WAC	ENST00000651598.1 link	c.-76+19G>T	intron_variant	Intron 2 of 5			ENSP00000498480.1	A0A494C0C1

Frequencies

GnomAD3 genomes

AF:

0.00373

AC:

567

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00557

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00382

AC:

777

AN:

203196

Hom.:

AF XY:

0.00382

AC XY:

427

AN XY:

111906

show subpopulations

Gnomad AFR exome

AF:

0.00143

Gnomad AMR exome

AF:

0.00279

Gnomad ASJ exome

AF:

0.00202

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000643

Gnomad FIN exome

AF:

0.00305

Gnomad NFE exome

AF:

0.00620

Gnomad OTH exome

AF:

0.00500

GnomAD4 exome

AF:

0.00583

AC:

8290

AN:

1421654

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

3991

AN XY:

706874

show subpopulations

Gnomad4 AFR exome

AF:

0.000647

Gnomad4 AMR exome

AF:

0.00272

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.0000279

Gnomad4 SAS exome

AF:

0.00133

Gnomad4 FIN exome

AF:

0.00354

Gnomad4 NFE exome

AF:

0.00691

Gnomad4 OTH exome

AF:

0.00432

GnomAD4 genome

AF:

0.00372

AC:

566

AN:

152318

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00557

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00531

Hom.:

Bravo

AF:

0.00381

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 03, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.92

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over