rs750650734

Variant names:

• chr9-14884-C-A
• rs750650734
• NM_001378090.1:c.1321G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-14884-C-A
• chr9-14884-C-G
• chr9-14884-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378090.1(WASHC1):​c.1321G>T​(p.Val441Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000243 in 1,236,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. 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. V441M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: WASHC1 NM_001378090.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11443925).

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.1321G>T	p.Val441Leu	missense	Exon 11 of 11	NP_001365019.1	A8K0Z3
	WASHC1	NM_182905.6		c.1321G>T	p.Val441Leu	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.1321G>T	p.Val441Leu	missense	Exon 11 of 11	ENSP00000512441.1	A8K0Z3
	WASHC1	ENST00000442898.5	TSL:2	c.1321G>T	p.Val441Leu	missense	Exon 11 of 11	ENSP00000485627.1	A8K0Z3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000538 AC: 1 AN: 186004 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000710

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000243 AC: 3 AN: 1236604 Hom.: 0 Cov.: 37 AF XY: 0.00000324 AC XY: 2 AN XY: 617308

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19738

American (AMR) AF: 0.0000256 AC: 1 AN: 39030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22374

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35864

South Asian (SAS) AF: 0.00 AC: 0 AN: 74660

European-Finnish (FIN) AF: 0.0000214 AC: 1 AN: 46672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3432

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 943866

Other (OTH) AF: 0.00 AC: 0 AN: 50968

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000568638), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.0039	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.11	T
MutationAssessor	Benign	-0.17	N
PhyloP100		3.6
PrimateAI	Uncertain	0.77	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.28
MVP		0.21
GERP RS		0.0057
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.031
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs750650734; hg19: chr9-14884;