chr8-125043839-C-G

Variant names:

• chr8-125043839-C-G
• NM_014846.4:c.2836G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014846.4(WASHC5):​c.2836G>C​(p.Glu946Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,346 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WASHC5 NM_014846.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WASHC5	NM_014846.4	c.2836G>C	p.Glu946Gln	missense_variant	Exon 23 of 29	ENST00000318410.12	NP_055661.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASHC5	ENST00000318410.12	c.2836G>C	p.Glu946Gln	missense_variant	Exon 23 of 29	1	NM_014846.4	ENSP00000318016.7
WASHC5	ENST00000517845.5	c.2392G>C	p.Glu798Gln	missense_variant	Exon 21 of 27	2		ENSP00000429676.1
WASHC5-AS1	ENST00000519140.1	n.97-660C>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457346 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725340

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Uncertain	0.31	D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.53
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.098	T;T
Polyphen		0.22	B;P
Vest4		0.44
MutPred		0.62		Gain of MoRF binding (P = 0.0194);.;
MVP		0.85
MPC		0.65
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.19
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-126056081;