8-125032022-A-C

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.3335+219T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,976 control chromosomes in the GnomAD database, including 13,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (13390 hom., cov: 31)
• Consequence: WASHC5 NM_014846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

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=-0.9).
• BP6: Variant 8-125032022-A-C is Benign according to our data. Variant chr8-125032022-A-C is described in ClinVar as [Benign]. Clinvar id is 1293643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WASHC5	NM_014846.4	c.3335+219T>G		intron_variant		ENST00000318410.12
WASHC5	NM_001330609.2	c.2891+219T>G		intron_variant
WASHC5	XM_047422502.1	c.3335+219T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASHC5	ENST00000318410.12	c.3335+219T>G		intron_variant		1	NM_014846.4	P1
WASHC5	ENST00000517845.5	c.2891+219T>G		intron_variant		2
WASHC5	ENST00000519042.2	n.474+219T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58494 AN: 151858 Hom.: 13347 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.385 AC: 58586 AN: 151976 Hom.: 13390 Cov.: 31 AF XY: 0.391 AC XY: 29066 AN XY: 74274

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.389

Alfa AF: 0.233 Hom.: 779

Bravo AF: 0.407

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	-0.90
Cadd	Benign	11
Dann	Benign	0.73

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: rs3750237; hg19: chr8-126044264; COSMIC: COSV59194900;