chr9-15937-C-G

Variant names:

• chr9-15937-C-G
• rs564190728
• NM_001378090.1:c.1167G>C

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.1167G>C​(p.Glu389Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,260,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: WASHC1 NM_001378090.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.90
• 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=0.22463986).

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.1167G>C	p.Glu389Asp	missense	Exon 9 of 11	NP_001365019.1	A8K0Z3
	WASHC1	NM_182905.6		c.1167G>C	p.Glu389Asp	missense	Exon 9 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.1167G>C	p.Glu389Asp	missense	Exon 9 of 11	ENSP00000512441.1	A8K0Z3
	WASHC1	ENST00000442898.5	TSL:2	c.1167G>C	p.Glu389Asp	missense	Exon 9 of 11	ENSP00000485627.1	A8K0Z3
	WASHC1	ENST00000696150.1		n.1431G>C		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1260668 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 629914

African (AFR) AF: 0.00 AC: 0 AN: 23006

American (AMR) AF: 0.00 AC: 0 AN: 40500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23320

East Asian (EAS) AF: 0.0000270 AC: 1 AN: 37034

South Asian (SAS) AF: 0.00 AC: 0 AN: 77610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 957002

Other (OTH) AF: 0.00 AC: 0 AN: 52110

GnomAD4 genome Cov.: 22

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	0.26
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.049	T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.22	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.9
PrimateAI	Pathogenic	0.86	D
Sift4G	Benign	0.48	T
Polyphen		0.51	P
Vest4		0.41
MVP		0.24
GERP RS		1.3
Varity_R		0.084
gMVP		0.21

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

Other links and lift over

dbSNP: rs564190728; hg19: chr9-15937;