rs7812319

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014846.4(WASHC5):c.597A>G(p.Pro199Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 1,613,884 control chromosomes in the GnomAD database, including 1,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 128 hom., cov: 31)

Exomes 𝑓: 0.031 ( 1613 hom. )

Consequence

WASHC5
NM_014846.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.638

Publications

9 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

Ritscher-Schinzel syndrome 1
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
hereditary spastic paraplegia 8
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Ritscher-Schinzel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WASHC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 8-125078852-T-C is Benign according to our data. Variant chr8-125078852-T-C is described in ClinVar as Benign. ClinVar VariationId is 129377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.638 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 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.597A>G	p.Pro199Pro	synonymous	Exon 6 of 29	NP_055661.3
	WASHC5	NM_001330609.2		c.153A>G	p.Pro51Pro	synonymous	Exon 5 of 28	NP_001317538.1	E7EQI7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WASHC5	ENST00000318410.12	TSL:1 MANE Select	c.597A>G	p.Pro199Pro	synonymous	Exon 6 of 29	ENSP00000318016.7	Q12768
WASHC5	ENST00000920325.1		c.597A>G	p.Pro199Pro	synonymous	Exon 6 of 29	ENSP00000590384.1
WASHC5	ENST00000890504.1		c.597A>G	p.Pro199Pro	synonymous	Exon 7 of 30	ENSP00000560563.1

Frequencies

GnomAD3 genomes

AF:

0.0285

AC:

4341

AN:

152070

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0283

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.0699

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0217

Gnomad OTH

AF:

0.0349

GnomAD2 exomes

AF:

0.0425

AC:

10682

AN:

251400

AF XY:

0.0470

show subpopulations

Gnomad AFR exome

AF:

0.0276

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.0758

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.0238

Gnomad OTH exome

AF:

0.0342

GnomAD4 exome

AF:

0.0315

AC:

46029

AN:

1461696

Hom.:

1613

Cov.:

AF XY:

0.0351

AC XY:

25556

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.0288

AC:

965

AN:

33478

American (AMR)

AF:

0.0135

AC:

604

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0162

AC:

424

AN:

26132

East Asian (EAS)

AF:

0.0640

AC:

2539

AN:

39690

South Asian (SAS)

AF:

0.152

AC:

13115

AN:

86250

European-Finnish (FIN)

AF:

0.0222

AC:

1185

AN:

53418

Middle Eastern (MID)

AF:

0.0558

AC:

322

AN:

5768

European-Non Finnish (NFE)

AF:

0.0223

AC:

24781

AN:

1111852

Other (OTH)

AF:

0.0347

AC:

2094

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2215

4430

6646

8861

11076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1048

2096

3144

4192

5240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0285

AC:

4337

AN:

152188

Hom.:

128

Cov.:

AF XY:

0.0310

AC XY:

2307

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0282

AC:

1172

AN:

41520

American (AMR)

AF:

0.0139

AC:

212

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3470

East Asian (EAS)

AF:

0.0695

AC:

359

AN:

5166

South Asian (SAS)

AF:

0.159

AC:

765

AN:

4816

European-Finnish (FIN)

AF:

0.0197

AC:

209

AN:

10614

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0217

AC:

1473

AN:

68000

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

192

384

576

768

960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0249

Hom.:

106

Bravo

AF:

0.0253

Asia WGS

AF:

0.120

AC:

419

AN:

3478

EpiCase

AF:

0.0245

EpiControl

AF:

0.0233

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Hereditary spastic paraplegia (1)

Hereditary spastic paraplegia 8 (1)

not provided (1)

Ritscher-Schinzel syndrome;C1863704:Hereditary spastic paraplegia 8 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over