Genetic Variant WASHC1:p.Glu389Glu (chr9-15937-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_001378090.1(WASHC1):c.1167G>A(p.Glu389Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,386,288 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 17 hom., cov: 22)

Exomes 𝑓: 0.00011 ( 16 hom. )

Consequence

WASHC1
NM_001378090.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

Publications

0 publications found

Variant links:

Genes affected

WASHC1 (HGNC:24361): (WASH complex subunit 1) Enables alpha-tubulin binding activity and ubiquitin protein ligase binding activity. Involved in several processes, including Arp2/3 complex-mediated actin nucleation; endosomal transport; and positive regulation of pseudopodium assembly. Located in early endosome. Part of WASH complex. Colocalizes with exocyst. [provided by Alliance of Genome Resources, Apr 2022]

WASHC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP7

Synonymous conserved (PhyloP=2.9 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 17 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378090.1. 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
	WASHC1	NM_001378090.1	MANE Select	c.1167G>A	p.Glu389Glu	synonymous	Exon 9 of 11	NP_001365019.1	A8K0Z3
	WASHC1	NM_182905.6		c.1167G>A	p.Glu389Glu	synonymous	Exon 9 of 11	NP_878908.4	A8K0Z3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WASHC1	ENST00000696149.1	MANE Select	c.1167G>A	p.Glu389Glu	synonymous	Exon 9 of 11	ENSP00000512441.1	A8K0Z3
WASHC1	ENST00000442898.5	TSL:2	c.1167G>A	p.Glu389Glu	synonymous	Exon 9 of 11	ENSP00000485627.1	A8K0Z3
WASHC1	ENST00000696150.1		n.1431G>A		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

164

AN:

125546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00565

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000455

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:

0.00

Gnomad OTH

AF:

0.000569

GnomAD2 exomes

AF:

0.000258

AC:

AN:

178238

AF XY:

0.000236

show subpopulations

Gnomad AFR exome

AF:

0.00604

Gnomad AMR exome

AF:

0.0000351

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000110

AC:

139

AN:

1260666

Hom.:

Cov.:

AF XY:

0.0000984

AC XY:

AN XY:

629910

show subpopulations

African (AFR)

AF:

0.00561

AC:

129

AN:

23004

American (AMR)

AF:

0.0000741

AC:

AN:

40500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23320

East Asian (EAS)

AF:

0.00

AC:

AN:

37034

South Asian (SAS)

AF:

0.00

AC:

AN:

77610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3560

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

957004

Other (OTH)

AF:

0.000134

AC:

AN:

52108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00131

AC:

164

AN:

125622

Hom.:

Cov.:

AF XY:

0.000978

AC XY:

AN XY:

61374

show subpopulations

African (AFR)

AF:

0.00563

AC:

157

AN:

27866

American (AMR)

AF:

0.000454

AC:

AN:

13216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3088

East Asian (EAS)

AF:

0.00

AC:

AN:

4820

South Asian (SAS)

AF:

0.00

AC:

AN:

4174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60356

Other (OTH)

AF:

0.000563

AC:

AN:

1776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00110

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

2.9

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

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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