8-125028383-G-A

Position:

• chr8-125028383-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014846.4(WASHC5):​c.3423+237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,178 control chromosomes in the GnomAD database, including 999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (999 hom., cov: 32)
• Consequence: WASHC5 NM_014846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-125028383-G-A is Benign according to our data. Variant chr8-125028383-G-A is described in ClinVar as [Benign]. Clinvar id is 1293644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WASHC5	NM_014846.4	c.3423+237C>T		intron_variant		ENST00000318410.12
WASHC5	NM_001330609.2	c.2979+237C>T		intron_variant
WASHC5	XM_047422502.1	c.3423+237C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASHC5	ENST00000318410.12	c.3423+237C>T		intron_variant		1	NM_014846.4	P1
WASHC5	ENST00000517845.5	c.2979+237C>T		intron_variant		2
WASHC5	ENST00000519042.2	n.562+237C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16070 AN: 152060 Hom.: 998 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0944

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0790

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.110

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16077 AN: 152178 Hom.: 999 Cov.: 32 AF XY: 0.102 AC XY: 7602 AN XY: 74402

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0942

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0245

Gnomad4 FIN AF: 0.0790

Gnomad4 NFE AF: 0.0900

Gnomad4 OTH AF: 0.108

Alfa AF: 0.104 Hom.: 140

Bravo AF: 0.110

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs57886679; hg19: chr8-126040625;