9-14886-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001378090.1(WASHC1):​c.1319G>T​(p.Arg440Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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 0.0 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WASHC1 NM_001378090.1 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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>T	p.Arg440Leu	missense	Exon 11 of 11	NP_001365019.1	A8K0Z3
	WASHC1	NM_182905.6		c.1319G>T	p.Arg440Leu	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>T	p.Arg440Leu	missense	Exon 11 of 11	ENSP00000512441.1	A8K0Z3
	WASHC1	ENST00000442898.5	TSL:2	c.1319G>T	p.Arg440Leu	missense	Exon 11 of 11	ENSP00000485627.1	A8K0Z3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 124552 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1235048 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 616514

African (AFR) AF: 0.00 AC: 0 AN: 19680

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

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35876

South Asian (SAS) AF: 0.00 AC: 0 AN: 74490

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: 0.00 AC: 0 AN: 942780

Other (OTH) AF: 0.00 AC: 0 AN: 50910

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 124552 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 60642

African (AFR) AF: 0.00 AC: 0 AN: 27490

American (AMR) AF: 0.00 AC: 0 AN: 13008

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4866

South Asian (SAS) AF: 0.00 AC: 0 AN: 4120

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60056

Other (OTH) AF: 0.00 AC: 0 AN: 1756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.27	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Uncertain	0.67	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.8
PrimateAI	Uncertain	0.72	T
Sift4G	Uncertain	0.010	D
Polyphen		0.68	P
Vest4		0.64
MVP		0.54
GERP RS		1.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.080
gMVP		0.38

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;