Variant 12-105115677-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015275.3(WASHC4):c.384G>T(p.Met128Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000649 in 1,609,670 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 5 hom. )

Consequence

WASHC4
NM_015275.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.98

Variant links:

Genes affected

WASHC4 (HGNC:29174): (WASH complex subunit 4) This gene encodes a component of the WASH complex, which functions in the intracellular transport of endosomes. Mutations in this gene have been detected in individuals with autosomal recessive cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

WASHC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009555548).

BP6

Variant 12-105115677-G-T is Benign according to our data. Variant chr12-105115677-G-T is described in ClinVar as [Benign]. Clinvar id is 732660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00325 (495/152138) while in subpopulation AFR AF= 0.011 (457/41534). AF 95% confidence interval is 0.0102. There are 2 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WASHC4	NM_015275.3 linkuse as main transcript	c.384G>T	p.Met128Ile	missense_variant	6/33	ENST00000332180.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASHC4	ENST00000332180.10 linkuse as main transcript	c.384G>T	p.Met128Ile	missense_variant	6/33	1	NM_015275.3	A1	Q2M389-1

Frequencies

GnomAD3 genomes

AF:

0.00323

AC:

491

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

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:

0.0000147

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.000858

AC:

214

AN:

249336

Hom.:

AF XY:

0.000658

AC XY:

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000377

AC:

550

AN:

1457532

Hom.:

Cov.:

AF XY:

0.000339

AC XY:

246

AN XY:

725434

show subpopulations

Gnomad4 AFR exome

AF:

0.0123

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00325

AC:

495

AN:

152138

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

249

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.000553

Hom.:

Bravo

AF:

0.00369

ESP6500AA

AF:

0.0112

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00101

AC:

122

Asia WGS

AF:

0.00145

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	WASHC4: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.022

T;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

0.011

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;T;T

MetaRNN

Benign

0.0096

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.4

N;N;.

REVEL

Benign

0.064

Sift

Benign

0.17

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.24, 0.22

MutPred

0.27

.;Gain of catalytic residue at A123 (P = 0);Gain of catalytic residue at A123 (P = 0);

MVP

0.24

MPC

0.19

ClinPred

0.024

GERP RS

6.0

Varity_R

0.17

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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