Variant chr10-28533531-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016628.5(WAC):c.-49C>G 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 0.0000391 in 1,229,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

WAC
NM_016628.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.701

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=-0.83).

BP6

Variant 10-28533531-C-G is Benign according to our data. Variant chr10-28533531-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1188283.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WAC	NM_016628.5 link	c.-49C>G		5_prime_UTR_premature_start_codon_gain_variant	1/14	ENST00000354911.9	NP_057712.2	Q9BTA9-1
WAC	NM_016628.5 link	c.-49C>G		5_prime_UTR_variant	1/14	ENST00000354911.9	NP_057712.2	Q9BTA9-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WAC	ENST00000354911 link	c.-49C>G	5_prime_UTR_premature_start_codon_gain_variant	1/14	1	NM_016628.5	ENSP00000346986.4	Q9BTA9-1
WAC	ENST00000651885 link	c.-49C>G	5_prime_UTR_premature_start_codon_gain_variant	1/5			ENSP00000498678.1	A0A494C0S5
WAC	ENST00000354911 link	c.-49C>G	5_prime_UTR_variant	1/14	1	NM_016628.5	ENSP00000346986.4	Q9BTA9-1
WAC	ENST00000651885 link	c.-49C>G	5_prime_UTR_variant	1/5			ENSP00000498678.1	A0A494C0S5
WAC	ENST00000428935.6 link	c.-94-467C>G	intron_variant		2		ENSP00000399706.3	A0A0A0MSR1
WAC	ENST00000651598.1 link	c.-112-467C>G	intron_variant				ENSP00000498480.1	A0A494C0C1

Frequencies

GnomAD3 genomes

AF:

0.0000403

AC:

AN:

148886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000449

Gnomad OTH

AF:

0.000488

GnomAD3 exomes

AF:

0.000150

AC:

AN:

173206

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

98258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000685

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000729

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.0000389

AC:

AN:

1080262

Hom.:

Cov.:

AF XY:

0.0000377

AC XY:

AN XY:

530236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000704

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000224

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.0000403

AC:

AN:

148886

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72522

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000449

Gnomad4 OTH

AF:

0.000488

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000117

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.62

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