8-125043973-G-GC

Variant names:

• chr8-125043973-G-GC
• rs11370883
• NM_014846.4:c.2770+18_2770+19insG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.333
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC5	NM_014846.4	MANE Select	c.2770+18_2770+19insG		intron	N/A	NP_055661.3
	WASHC5	NM_001330609.2		c.2326+18_2326+19insG		intron	N/A	NP_001317538.1	E7EQI7
	WASHC5-AS1	NR_170219.1		n.97-526_97-525insC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC5	ENST00000318410.12	TSL:1 MANE Select	c.2770+18_2770+19insG		intron	N/A	ENSP00000318016.7	Q12768
	WASHC5	ENST00000920325.1		c.2818+18_2818+19insG		intron	N/A	ENSP00000590384.1
	WASHC5	ENST00000890504.1		c.2770+18_2770+19insG		intron	N/A	ENSP00000560563.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152218 AN: 152226 Hom.: 76105 Cov.: 0

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

GnomAD2 exomes AF: 1.00 AC: 251327 AN: 251344 AF XY: 1.00

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 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.: 29 AF XY: 1.00 AC XY: 720739 AN XY: 720890

African (AFR) AF: 1.00 AC: 33148 AN: 33152

American (AMR) AF: 1.00 AC: 44704 AN: 44704

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26026 AN: 26026

East Asian (EAS) AF: 1.00 AC: 39608 AN: 39608

South Asian (SAS) AF: 1.00 AC: 85928 AN: 85930

European-Finnish (FIN) AF: 1.00 AC: 53410 AN: 53410

Middle Eastern (MID) AF: 1.00 AC: 5734 AN: 5734

European-Non Finnish (NFE) AF: 1.00 AC: 1098187 AN: 1098460

Other (OTH) AF: 1.00 AC: 59873 AN: 59876

GnomAD4 genome AF: 1.00 AC: 152336 AN: 152344 Hom.: 76164 Cov.: 0 AF XY: 1.00 AC XY: 74493 AN XY: 74494

African (AFR) AF: 1.00 AC: 41570 AN: 41570

American (AMR) AF: 1.00 AC: 15298 AN: 15298

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3470 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 1.00 AC: 4828 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68040 AN: 68048

Other (OTH) AF: 1.00 AC: 2116 AN: 2116

Alfa AF: 1.00 Hom.: 12693

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11370883; hg19: chr8-126056215;