NM_001005751.3:c.1144C>T

Variant names:

• chr10-50093881-C-T
• rs1157827955
• NM_001005751.3:c.1144C>T

Variant summary

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

The NM_001005751.3(WASHC2A):​c.1144C>T​(p.Pro382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000723 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WASHC2A NM_001005751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.763
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08005577).

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.1144C>T	p.Pro382Ser	missense	Exon 13 of 31	NP_001005751.1	Q641Q2-1
	WASHC2A	NM_001291398.2		c.1144C>T	p.Pro382Ser	missense	Exon 13 of 30	NP_001278327.1	Q641Q2-2
	WASHC2A	NM_001437388.1		c.1072C>T	p.Pro358Ser	missense	Exon 12 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.1144C>T	p.Pro382Ser	missense	Exon 13 of 31	ENSP00000282633.5	Q641Q2-1
	WASHC2A	ENST00000351071.11	TSL:1	c.1144C>T	p.Pro382Ser	missense	Exon 13 of 30	ENSP00000344037.6	Q641Q2-2
	WASHC2A	ENST00000314664.12	TSL:1	c.1144C>T	p.Pro382Ser	missense	Exon 13 of 29	ENSP00000314417.7	E7ESD2

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152042 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000293 AC: 2 AN: 68174 AF XY: 0.0000298

Gnomad AFR exome AF: 0.000167

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000206 AC: 3 AN: 1458080 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725416

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000300 AC: 1 AN: 33348

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110534

Other (OTH) AF: 0.0000166 AC: 1 AN: 60130

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152158 Hom.: 0 Cov.: 28 AF XY: 0.000134 AC XY: 10 AN XY: 74372

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000193 AC: 8 AN: 41520

American (AMR) AF: 0.000131 AC: 2 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2106

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	Benign	0.096
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.75	T
PhyloP100		0.76
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.17
Sift	Benign	0.11	T
Sift4G	Uncertain	0.044	D
Polyphen		0.049	B
Vest4		0.11
MutPred		0.18		Gain of phosphorylation at P382 (P = 0.0148)
MVP		0.15
ClinPred		0.086	T
GERP RS		3.9
Varity_R		0.095
gMVP		0.31
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1157827955; hg19: chr10-51853641;