10-45728918-C-G

Variant names:

• chr10-45728918-C-G
• NM_001330074.2:c.183C>G

Variant summary

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

The NM_001367411.1(WASHC2C):​c.-79C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,648 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WASHC2C NM_001367411.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.453
• Publications: 0 publications found

Genes affected

WASHC2C (HGNC:23414): (WASH complex subunit 2C) Enables phosphatidylinositol phosphate binding activity; phosphatidylinositol-3,4-bisphosphate binding activity; and retromer complex binding activity. Involved in several processes, including endosomal transport; negative regulation of barbed-end actin filament capping; and regulation of substrate adhesion-dependent cell spreading. Located in cytosol; early endosome; and nucleolus. Part of WASH complex. [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=0.19313398).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367411.1. 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
	WASHC2C	NM_001330074.2	MANE Select	c.183C>G	p.Ile61Met	missense	Exon 3 of 31	NP_001317003.1	Q9Y4E1-7
	WASHC2C	NM_001367411.1		c.-79C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 31	NP_001354340.1
	WASHC2C	NM_001367409.1		c.-79C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 30	NP_001354338.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC2C	ENST00000623400.4	TSL:1 MANE Select	c.183C>G	p.Ile61Met	missense	Exon 3 of 31	ENSP00000485513.1	Q9Y4E1-7
	WASHC2C	ENST00000374362.6	TSL:1	c.183C>G	p.Ile61Met	missense	Exon 3 of 30	ENSP00000363482.2	Q9Y4E1-4
	WASHC2C	ENST00000540872.6	TSL:1	c.183C>G	p.Ile61Met	missense	Exon 3 of 29	ENSP00000439811.1	Q9Y4E1-6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461648 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111840

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome Cov.: 31

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	Uncertain	0.34
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.45	T
PhyloP100		0.45
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.17
Sift	Benign	0.031	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.26		Gain of disorder (P = 0.0713)
MVP		0.21
ClinPred		0.89	D
GERP RS		4.0
Varity_R		0.43
gMVP		0.43
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr10-46224366;