9-15937-C-G

Position:

• chr9-15937-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

WASHC1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22463986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC1	NM_001378090.1	c.1167G>C	p.Glu389Asp	missense_variant	9/11	ENST00000696149.1	NP_001365019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASHC1	ENST00000696149.1	c.1167G>C	p.Glu389Asp	missense_variant	9/11		NM_001378090.1	ENSP00000512441.1
WASHC1	ENST00000442898.5	c.1167G>C	p.Glu389Asp	missense_variant	9/11	2		ENSP00000485627.1
WASHC1	ENST00000696150.1	n.1431G>C		non_coding_transcript_exon_variant	9/9

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000270

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

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 03, 2024

The c.1167G>C (p.E389D) alteration is located in exon 9 (coding exon 8) of the WASH1 gene. This alteration results from a G to C substitution at nucleotide position 1167, causing the glutamic acid (E) at amino acid position 389 to be replaced by an aspartic acid (D). 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	0.26
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
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-15937;