Variant chr8-125043973-G-GC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_014846.4(WASHC5):c.2770+18_2770+19insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,599,244 control chromosomes in the GnomAD database, including 799,332 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 76164 hom., cov: 0)

Exomes 𝑓: 1.0 ( 723168 hom. )

Consequence

WASHC5
NM_014846.4 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.333

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 links:

WASHC5-AS1 (HGNC:43440): (WASHC5 antisense RNA 1)

WASHC5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 8-125043973-G-GC is Benign according to our data. Variant chr8-125043973-G-GC is described in ClinVar as [Benign]. Clinvar id is 516650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC5	NM_014846.4 linkuse as main transcript	c.2770+18_2770+19insG		intron_variant		ENST00000318410.12	NP_055661.3
WASHC5-AS1	NR_170219.1 linkuse as main transcript	n.97-526_97-525insC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
WASHC5	ENST00000318410.12 linkuse as main transcript	c.2770+18_2770+19insG	intron_variant	1	NM_014846.4	ENSP00000318016	P1
WASHC5-AS1	ENST00000519140.1 linkuse as main transcript	n.97-526_97-525insC	intron_variant, non_coding_transcript_variant	4
WASHC5	ENST00000517845.5 linkuse as main transcript	c.2326+18_2326+19insG	intron_variant	2		ENSP00000429676

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

152218

AN:

152226

Hom.:

76105

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD3 exomes

AF:

1.00

AC:

251327

AN:

251344

Hom.:

125655

AF XY:

1.00

AC XY:

135846

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1446618

AN:

1446900

Hom.:

723168

Cov.:

AF XY:

1.00

AC XY:

720739

AN XY:

720890

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

1.00

AC:

152336

AN:

152344

Hom.:

76164

Cov.:

AF XY:

1.00

AC XY:

74493

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

1.00

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

1.00

Hom.:

12693

Bravo

AF:

1.00

Asia WGS

AF:

1.00

AC:

3478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

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