Genetic Variant WAC:c.-136A>C (chr10-28533444-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016628.5(WAC):c.-136A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 278,812 control chromosomes in the GnomAD database, including 139,403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 74747 hom., cov: 29)

Exomes 𝑓: 1.0 ( 64656 hom. )

Consequence

WAC
NM_016628.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 10-28533444-A-C is Benign according to our data. Variant chr10-28533444-A-C is described in ClinVar as [Benign]. Clinvar id is 1271155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAC	NM_016628.5 link	c.-136A>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14	ENST00000354911.9	NP_057712.2	Q9BTA9-1
WAC	NM_016628.5 link	c.-136A>C		5_prime_UTR_variant	Exon 1 of 14	ENST00000354911.9	NP_057712.2	Q9BTA9-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WAC	ENST00000354911 link	c.-136A>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14	1	NM_016628.5	ENSP00000346986.4	Q9BTA9-1
WAC	ENST00000354911 link	c.-136A>C	5_prime_UTR_variant	Exon 1 of 14	1	NM_016628.5	ENSP00000346986.4	Q9BTA9-1
WAC	ENST00000428935.6 link	c.-95+437A>C	intron_variant	Intron 1 of 7	2		ENSP00000399706.3	A0A0A0MSR1
WAC	ENST00000651598.1 link	c.-113+437A>C	intron_variant	Intron 1 of 5			ENSP00000498480.1	A0A494C0C1
WAC	ENST00000651885.1 link	c.-136A>C	upstream_gene_variant				ENSP00000498678.1	A0A494C0S5

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

149386

AN:

149386

Hom.:

74693

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

129314

AN:

129318

Hom.:

64656

Cov.:

AF XY:

1.00

AC XY:

63874

AN XY:

63874

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

1.00

AC:

149494

AN:

149494

Hom.:

74747

Cov.:

AF XY:

1.00

AC XY:

72914

AN XY:

72914

show subpopulations

Gnomad4 AFR

AF:

1.00

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

1.00

Hom.:

8743

Bravo

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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