10-45750100-C-A

Variant names:

• chr10-45750100-C-A
• rs782647105
• NM_001330074.2:c.737C>A

Variant summary

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

The NM_001330074.2(WASHC2C):​c.737C>A​(p.Thr246Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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. T246I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 25)
• Consequence: WASHC2C NM_001330074.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• 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=0.09217012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330074.2. 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.737C>A	p.Thr246Asn	missense	Exon 9 of 31	NP_001317003.1	Q9Y4E1-7
	WASHC2C	NM_001367395.1		c.737C>A	p.Thr246Asn	missense	Exon 9 of 31	NP_001354324.1
	WASHC2C	NM_015262.3		c.737C>A	p.Thr246Asn	missense	Exon 9 of 30	NP_056077.2	Q9Y4E1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC2C	ENST00000623400.4	TSL:1 MANE Select	c.737C>A	p.Thr246Asn	missense	Exon 9 of 31	ENSP00000485513.1	Q9Y4E1-7
	WASHC2C	ENST00000374362.6	TSL:1	c.737C>A	p.Thr246Asn	missense	Exon 9 of 30	ENSP00000363482.2	Q9Y4E1-4
	WASHC2C	ENST00000540872.6	TSL:1	c.737C>A	p.Thr246Asn	missense	Exon 9 of 29	ENSP00000439811.1	Q9Y4E1-6

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.20
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Benign	0.10	T
Sift4G	Benign	0.15	T
Polyphen		0.58	P
Vest4		0.19
MutPred		0.11		Loss of glycosylation at T246 (P = 0.0383)
MVP		0.12
ClinPred		0.39	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.059
gMVP		0.041
Mutation Taster		=95/5	polymorphism

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: rs782647105; hg19: chr10-46245548;