9-14886-C-T

Variant names:

• chr9-14886-C-T
• rs566352560
• NM_001378090.1:c.1319G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001378090.1(WASHC1):​c.1319G>A​(p.Arg440His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000875 in 1,359,608 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R440C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00047 (2 hom., cov: 24)
  • Exomes 𝑓: 0.000049 (3 hom.)
• Consequence: WASHC1 NM_001378090.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042898).
• BS2: High Homozygotes in GnomAd4 at 2 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.1319G>A	p.Arg440His	missense	Exon 11 of 11	NP_001365019.1	A8K0Z3
	WASHC1	NM_182905.6		c.1319G>A	p.Arg440His	missense	Exon 11 of 11	NP_878908.4	A8K0Z3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC1	ENST00000696149.1	MANE Select	c.1319G>A	p.Arg440His	missense	Exon 11 of 11	ENSP00000512441.1	A8K0Z3
	WASHC1	ENST00000442898.5	TSL:2	c.1319G>A	p.Arg440His	missense	Exon 11 of 11	ENSP00000485627.1	A8K0Z3

Frequencies

GnomAD3 genomes AF: 0.000474 AC: 59 AN: 124538 Hom.: 2 Cov.: 24

Gnomad AFR AF: 0.00182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000384

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: 0.0000500

Gnomad OTH AF: 0.000569

GnomAD2 exomes AF: 0.0000436 AC: 8 AN: 183546 AF XY: 0.0000600

Gnomad AFR exome AF: 0.000697

Gnomad AMR exome AF: 0.0000356

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000241

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 60 AN: 1235020 Hom.: 3 Cov.: 37 AF XY: 0.0000454 AC XY: 28 AN XY: 616490

African (AFR) AF: 0.00153 AC: 30 AN: 19672

American (AMR) AF: 0.00 AC: 0 AN: 38922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22358

East Asian (EAS) AF: 0.0000836 AC: 3 AN: 35874

South Asian (SAS) AF: 0.0000940 AC: 7 AN: 74486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3420

European-Non Finnish (NFE) AF: 0.0000148 AC: 14 AN: 942766

Other (OTH) AF: 0.000118 AC: 6 AN: 50910

GnomAD4 genome AF: 0.000474 AC: 59 AN: 124588 Hom.: 2 Cov.: 24 AF XY: 0.000527 AC XY: 32 AN XY: 60700

African (AFR) AF: 0.00182 AC: 50 AN: 27542

American (AMR) AF: 0.000384 AC: 5 AN: 13028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3064

East Asian (EAS) AF: 0.00 AC: 0 AN: 4854

South Asian (SAS) AF: 0.00 AC: 0 AN: 4108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.0000500 AC: 3 AN: 60044

Other (OTH) AF: 0.000562 AC: 1 AN: 1778

Alfa AF: 0.000291 Hom.: 0

ExAC AF: 0.0000311 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.043	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.8
PrimateAI	Uncertain	0.72	T
Sift4G	Benign	0.083	T
Polyphen		0.0090	B
Vest4		0.49
MVP		0.23
GERP RS		1.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.028
gMVP		0.29

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

Other links and lift over

dbSNP: rs566352560; hg19: chr9-14886; COSMIC: COSV57924969; COSMIC: COSV57924969;