GeneBe

NM_015275.3:c.2132dupT

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_015275.3(WASHC4):​c.2132dupT​(p.Ser712LeufsTer13) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

WASHC4
NM_015275.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.51

Publications

1 publications found
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 Gene-Disease associations (from GenCC):
  • autosomal recessive non-syndromic intellectual disability
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • intellectual disability, autosomal recessive 43
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
  • schizophrenia
    Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WASHC4NM_015275.3 linkc.2132dupT p.Ser712LeufsTer13 frameshift_variant Exon 21 of 33 ENST00000332180.10 NP_056090.1 Q2M389-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WASHC4ENST00000332180.10 linkc.2132dupT p.Ser712LeufsTer13 frameshift_variant Exon 21 of 33 1 NM_015275.3 ENSP00000328062.6 Q2M389-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00000401
AC:
1
AN:
249358
AF XY:
0.00000739
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1461522
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727062
African (AFR)
AF:
0.00
AC:
0
AN:
33468
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39654
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86244
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111756
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.5
Mutation Taster
=7/193
disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs1236210910; hg19: chr12-105538179; COSMIC: COSV59889324; COSMIC: COSV59889324; API