Genetic Variant NM_016628.5:c.275-13750C>T (chr10-28569649-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016628.5(WAC):c.275-13750C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,928 control chromosomes in the GnomAD database, including 25,857 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 25857 hom., cov: 32)

Consequence

WAC
NM_016628.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.252

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

DeSanto-Shinawi syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
DeSanto-Shinawi syndrome due to WAC point mutation
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Illumina

WAC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAC	NM_016628.5 link	c.275-13750C>T		intron_variant	Intron 3 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.275-13750C>T	intron_variant	Intron 3 of 13	1	NM_016628.5	ENSP00000346986.4	Q9BTA9-1
WAC	ENST00000428935.6 link	c.140-13750C>T	intron_variant	Intron 3 of 7	2		ENSP00000399706.3	A0A0A0MSR1
WAC	ENST00000651885.1 link	c.293-13750C>T	intron_variant	Intron 3 of 4			ENSP00000498678.1	A0A494C0S5
WAC	ENST00000651598.1 link	c.140-13750C>T	intron_variant	Intron 3 of 5			ENSP00000498480.1	A0A494C0C1

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87567

AN:

151810

Hom.:

25820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.683

Gnomad SAS

AF:

0.670

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.659

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.577

AC:

87658

AN:

151928

Hom.:

25857

Cov.:

AF XY:

0.579

AC XY:

42944

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.672

AC:

27853

AN:

41434

American (AMR)

AF:

0.613

AC:

9348

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1974

AN:

3468

East Asian (EAS)

AF:

0.683

AC:

3526

AN:

5164

South Asian (SAS)

AF:

0.671

AC:

3227

AN:

4810

European-Finnish (FIN)

AF:

0.433

AC:

4558

AN:

10530

Middle Eastern (MID)

AF:

0.661

AC:

193

AN:

292

European-Non Finnish (NFE)

AF:

0.521

AC:

35382

AN:

67954

Other (OTH)

AF:

0.577

AC:

1218

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1871

3742

5612

7483

9354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.564

Hom.:

4772

Bravo

AF:

0.592

Asia WGS

AF:

0.676

AC:

2352

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.4

(source)

DANN

Benign

0.49

PhyloP100

-0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over