9-14865-G-C

Position:

• chr9-14865-G-C

Variant summary

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

The NM_001378090.1(WASHC1):​c.1340C>G​(p.Pro447Arg) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WASHC1 NM_001378090.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1	c.1340C>G	p.Pro447Arg	missense_variant	11/11	ENST00000696149.1	NP_001365019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASHC1	ENST00000696149.1	c.1340C>G	p.Pro447Arg	missense_variant	11/11		NM_001378090.1	ENSP00000512441.1
WASHC1	ENST00000442898.5	c.1340C>G	p.Pro447Arg	missense_variant	11/11	2		ENSP00000485627.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 53 AN: 125312 Hom.: 0 Cov.: 24 FAILED QC

Gnomad AFR AF: 0.000211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00146

Gnomad ASJ AF: 0.000326

Gnomad EAS AF: 0.00233

Gnomad SAS AF: 0.000245

Gnomad FIN AF: 0.000324

Gnomad MID AF: 0.00360

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.00114

GnomAD3 exomes AF: 0.000430 AC: 88 AN: 204786 Hom.: 0 AF XY: 0.000322 AC XY: 36 AN XY: 111920

Gnomad AFR exome AF: 0.000336

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.000119

Gnomad EAS exome AF: 0.000834

Gnomad SAS exome AF: 0.000551

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000227

Gnomad OTH exome AF: 0.000196

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000162 AC: 209 AN: 1286896 Hom.: 0 Cov.: 37 AF XY: 0.000187 AC XY: 120 AN XY: 641326

Gnomad4 AFR exome AF: 0.000203

Gnomad4 AMR exome AF: 0.000398

Gnomad4 ASJ exome AF: 0.0000436

Gnomad4 EAS exome AF: 0.00117

Gnomad4 SAS exome AF: 0.000776

Gnomad4 FIN exome AF: 0.000128

Gnomad4 NFE exome AF: 0.0000703

Gnomad4 OTH exome AF: 0.000152

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000423 AC: 53 AN: 125378 Hom.: 0 Cov.: 24 AF XY: 0.000458 AC XY: 28 AN XY: 61084

Gnomad4 AFR AF: 0.000211

Gnomad4 AMR AF: 0.00146

Gnomad4 ASJ AF: 0.000326

Gnomad4 EAS AF: 0.00233

Gnomad4 SAS AF: 0.000245

Gnomad4 FIN AF: 0.000324

Gnomad4 NFE AF: 0.000150

Gnomad4 OTH AF: 0.00112

Alfa AF: 0.000558 Hom.: 1

ExAC AF: 0.000140 AC: 15

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

The c.1340C>G (p.P447R) alteration is located in exon 11 (coding exon 10) of the WASH1 gene. This alteration results from a C to G substitution at nucleotide position 1340, causing the proline (P) at amino acid position 447 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.29	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Uncertain	0.68	D
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Pathogenic	0.83	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.72
MVP		0.37
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs766152762; hg19: chr9-14865; COSMIC: COSV57924354; COSMIC: COSV57924354;