8-125024346-AAC-A

Position:

• chr8-125024346-AAC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014846.4(WASHC5):​c.*269_*270del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 514,106 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (1 hom.)
• Consequence: WASHC5 NM_014846.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.10

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 -10 ACMG points.

• BP6: Variant 8-125024346-AAC-A is Benign according to our data. Variant chr8-125024346-AAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 361706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00744 (1134/152342) while in subpopulation AFR AF= 0.0256 (1064/41562). AF 95% confidence interval is 0.0243. There are 8 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WASHC5	NM_014846.4	c.*269_*270del		3_prime_UTR_variant	29/29	ENST00000318410.12
WASHC5	NM_001330609.2	c.*269_*270del		3_prime_UTR_variant	28/28
WASHC5	XM_047422502.1	c.*269_*270del		3_prime_UTR_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASHC5	ENST00000318410.12	c.*269_*270del		3_prime_UTR_variant	29/29	1	NM_014846.4	P1
WASHC5	ENST00000517845.5	c.*269_*270del		3_prime_UTR_variant	27/27	2
WASHC5	ENST00000519042.2	n.888_889del		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.00744 AC: 1133 AN: 152224 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

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: 0.000103

Gnomad OTH AF: 0.00716

GnomAD4 exome AF: 0.000915 AC: 331 AN: 361764 Hom.: 1 AF XY: 0.000754 AC XY: 145 AN XY: 192238

Gnomad4 AFR exome AF: 0.0241

Gnomad4 AMR exome AF: 0.00220

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000196

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000372

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00744 AC: 1134 AN: 152342 Hom.: 8 Cov.: 32 AF XY: 0.00720 AC XY: 536 AN XY: 74494

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.00313

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.00512 Hom.: 1

Bravo AF: 0.00842

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spastic paraplegia, autosomal dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs199912701; hg19: chr8-126036588;