chr9-14821-C-T

Variant names:

• chr9-14821-C-T
• rs761521000
• NM_001378090.1:c.1384G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001378090.1(WASHC1):​c.1384G>A​(p.Asp462Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,528,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: WASHC1 NM_001378090.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36650532).

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.1384G>A	p.Asp462Asn	missense	Exon 11 of 11	NP_001365019.1	A8K0Z3
	WASHC1	NM_182905.6		c.1384G>A	p.Asp462Asn	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.1384G>A	p.Asp462Asn	missense	Exon 11 of 11	ENSP00000512441.1	A8K0Z3
	WASHC1	ENST00000442898.5	TSL:2	c.1384G>A	p.Asp462Asn	missense	Exon 11 of 11	ENSP00000485627.1	A8K0Z3

Frequencies

GnomAD3 genomes AF: 0.000111 AC: 16 AN: 144122 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000681

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: 0.000152

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000153 AC: 32 AN: 209080 AF XY: 0.000201

Gnomad AFR exome AF: 0.000303

Gnomad AMR exome AF: 0.0000960

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.000192

GnomAD4 exome AF: 0.000173 AC: 240 AN: 1384738 Hom.: 0 Cov.: 39 AF XY: 0.000177 AC XY: 122 AN XY: 690436

African (AFR) AF: 0.000198 AC: 6 AN: 30298

American (AMR) AF: 0.0000920 AC: 4 AN: 43470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24744

East Asian (EAS) AF: 0.00 AC: 0 AN: 39168

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83262

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50876

Middle Eastern (MID) AF: 0.000256 AC: 1 AN: 3906

European-Non Finnish (NFE) AF: 0.000203 AC: 214 AN: 1051864

Other (OTH) AF: 0.000227 AC: 13 AN: 57150

GnomAD4 genome AF: 0.000111 AC: 16 AN: 144234 Hom.: 0 Cov.: 31 AF XY: 0.0000711 AC XY: 5 AN XY: 70342

African (AFR) AF: 0.000134 AC: 5 AN: 37292

American (AMR) AF: 0.0000681 AC: 1 AN: 14694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3352

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000152 AC: 10 AN: 65810

Other (OTH) AF: 0.00 AC: 0 AN: 1966

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000127 AC: 14

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	0.12
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.37	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		3.5
PrimateAI	Uncertain	0.65	T
Sift4G	Uncertain	0.019	D
Polyphen		0.98	D
Vest4		0.33
MVP		0.23
GERP RS		1.2
Varity_R		0.056
gMVP		0.46

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: rs761521000; hg19: chr9-14821;