NM_001005751.3:c.1031C>A

Variant names:

• chr10-50093295-C-A
• rs1443043282
• NM_001005751.3:c.1031C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001005751.3(WASHC2A):​c.1031C>A​(p.Pro344His) variant causes a missense change. The variant allele was found at a frequency of 0.000032 in 1,251,212 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P344L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 16)
  • Exomes 𝑓: 0.000032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WASHC2A NM_001005751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03
• Publications: 0 publications found

Genes affected

WASHC2A (HGNC:23416): (WASH complex subunit 2A) Predicted to enable phosphatidylinositol phosphate binding activity and retromer complex binding activity. Involved in protein localization to endosome. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39119413).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005751.3. 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
	WASHC2A	NM_001005751.3	MANE Select	c.1031C>A	p.Pro344His	missense	Exon 12 of 31	NP_001005751.1	Q641Q2-1
	WASHC2A	NM_001291398.2		c.1031C>A	p.Pro344His	missense	Exon 12 of 30	NP_001278327.1	Q641Q2-2
	WASHC2A	NM_001437388.1		c.959C>A	p.Pro320His	missense	Exon 11 of 30	NP_001424317.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC2A	ENST00000282633.10	TSL:1 MANE Select	c.1031C>A	p.Pro344His	missense	Exon 12 of 31	ENSP00000282633.5	Q641Q2-1
	WASHC2A	ENST00000351071.11	TSL:1	c.1031C>A	p.Pro344His	missense	Exon 12 of 30	ENSP00000344037.6	Q641Q2-2
	WASHC2A	ENST00000314664.12	TSL:1	c.1031C>A	p.Pro344His	missense	Exon 12 of 29	ENSP00000314417.7	E7ESD2

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 4 AN: 120792 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000656

GnomAD2 exomes AF: 0.0000171 AC: 1 AN: 58478 AF XY: 0.0000343

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000506

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000320 AC: 40 AN: 1251212 Hom.: 0 Cov.: 21 AF XY: 0.0000270 AC XY: 17 AN XY: 628928

African (AFR) AF: 0.00 AC: 0 AN: 31792

American (AMR) AF: 0.00 AC: 0 AN: 40236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22496

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.00 AC: 0 AN: 81580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3522

European-Non Finnish (NFE) AF: 0.0000399 AC: 37 AN: 928390

Other (OTH) AF: 0.0000567 AC: 3 AN: 52880

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000331 AC: 4 AN: 120792 Hom.: 0 Cov.: 16 AF XY: 0.0000346 AC XY: 2 AN XY: 57724

African (AFR) AF: 0.00 AC: 0 AN: 36538

American (AMR) AF: 0.000295 AC: 3 AN: 10164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 4892

South Asian (SAS) AF: 0.00 AC: 0 AN: 3534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53340

Other (OTH) AF: 0.000656 AC: 1 AN: 1524

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	-0.023	T
PhyloP100		6.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.26		Loss of catalytic residue at P343 (P = 0.0131)
MVP		0.21
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.82
gMVP		0.35
Mutation Taster		=84/16	polymorphism

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: rs1443043282; hg19: chr10-51853055;