8-125043846-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_014846.4(WASHC5):​c.2829G>A​(p.Ala943=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,611,172 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

WASHC5
NM_014846.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.145
Variant links:
Genes affected
WASHC5 (HGNC:28984): (WASH complex subunit 5) This gene encodes a 134 kDa protein named strumpellin that is predicted to have multiple transmembrane domains and a spectrin-repeat-containing domain. This ubiquitously expressed gene has its highest expression in skeletal muscle. The protein is named for Strumpell disease; a form of hereditary spastic paraplegia (HSP). Spastic paraplegias are a diverse group of disorders in which the autosomal dominant forms are characterized by progressive, lower extremity spasticity caused by axonal degeneration in the terminal portions of the longest descending and ascending corticospinal tracts. More than 30 loci (SPG1-33) have been implicated in hereditary spastic paraplegia diseases. [provided by RefSeq, Aug 2009]
WASHC5-AS1 (HGNC:43440): (WASHC5 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 8-125043846-C-T is Benign according to our data. Variant chr8-125043846-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 390766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.145 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WASHC5NM_014846.4 linkuse as main transcriptc.2829G>A p.Ala943= synonymous_variant 23/29 ENST00000318410.12 NP_055661.3
WASHC5-AS1NR_170219.1 linkuse as main transcriptn.97-653C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WASHC5ENST00000318410.12 linkuse as main transcriptc.2829G>A p.Ala943= synonymous_variant 23/291 NM_014846.4 ENSP00000318016 P1
WASHC5-AS1ENST00000519140.1 linkuse as main transcriptn.97-653C>T intron_variant, non_coding_transcript_variant 4
WASHC5ENST00000517845.5 linkuse as main transcriptc.2385G>A p.Ala795= synonymous_variant 21/272 ENSP00000429676

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152132
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000756
AC:
19
AN:
251236
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135788
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000126
AC:
184
AN:
1458922
Hom.:
1
Cov.:
30
AF XY:
0.000131
AC XY:
95
AN XY:
726018
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
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:
0.000156
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152250
Hom.:
0
Cov.:
33
AF XY:
0.0000940
AC XY:
7
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.000140
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 05, 2024- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2022WASHC5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
10
DANN
Benign
0.77

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.

Other links and lift over

dbSNP: rs369339497; hg19: chr8-126056088; COSMIC: COSV100572517; COSMIC: COSV100572517; API