8-125044113-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The ENST00000318410.12(WASHC5):​c.2668-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000495 in 1,486,882 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 1 hom. )

Consequence

WASHC5
ENST00000318410.12 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.416
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 8-125044113-G-A is Benign according to our data. Variant chr8-125044113-G-A is described in ClinVar as [Benign]. Clinvar id is 1599873.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00051 (681/1334694) while in subpopulation NFE AF= 0.000637 (635/996900). AF 95% confidence interval is 0.000596. There are 1 homozygotes in gnomad4_exome. There are 300 alleles in male gnomad4_exome subpopulation. Median coverage is 20. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WASHC5NM_014846.4 linkuse as main transcriptc.2668-19C>T intron_variant ENST00000318410.12 NP_055661.3
WASHC5-AS1NR_170219.1 linkuse as main transcriptn.97-386G>A 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.2668-19C>T intron_variant 1 NM_014846.4 ENSP00000318016 P1
WASHC5-AS1ENST00000519140.1 linkuse as main transcriptn.97-386G>A intron_variant, non_coding_transcript_variant 4
WASHC5ENST00000517845.5 linkuse as main transcriptc.2224-19C>T intron_variant 2 ENSP00000429676

Frequencies

GnomAD3 genomes
AF:
0.000362
AC:
55
AN:
152070
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000459
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:
0.000515
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000351
AC:
87
AN:
247526
Hom.:
0
AF XY:
0.000336
AC XY:
45
AN XY:
134000
show subpopulations
Gnomad AFR exome
AF:
0.000189
Gnomad AMR exome
AF:
0.000233
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:
0.000628
Gnomad OTH exome
AF:
0.000993
GnomAD4 exome
AF:
0.000510
AC:
681
AN:
1334694
Hom.:
1
Cov.:
20
AF XY:
0.000447
AC XY:
300
AN XY:
670954
show subpopulations
Gnomad4 AFR exome
AF:
0.0000969
Gnomad4 AMR exome
AF:
0.000270
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000120
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000637
Gnomad4 OTH exome
AF:
0.000517
GnomAD4 genome
AF:
0.000361
AC:
55
AN:
152188
Hom.:
1
Cov.:
32
AF XY:
0.000282
AC XY:
21
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000515
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000466
Hom.:
0
Bravo
AF:
0.000385

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 05, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
3.8
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.

Other links and lift over

dbSNP: rs368313044; hg19: chr8-126056355; API