chr10-45743424-T-C

Variant names:

• chr10-45743424-T-C
• rs368045657
• NM_001330074.2:c.563T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001367412.1(WASHC2C):​c.-17T>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000181 in 1,611,914 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: WASHC2C NM_001367412.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40797055).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367412.1. 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.563T>C	p.Ile188Thr	missense	Exon 6 of 31	NP_001317003.1	Q9Y4E1-7
	WASHC2C	NM_001367412.1		c.-17T>C		5_prime_UTR_premature_start_codon_gain	Exon 7 of 32	NP_001354341.1
	WASHC2C	NM_001367402.1		c.-17T>C		5_prime_UTR_premature_start_codon_gain	Exon 7 of 31	NP_001354331.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC2C	ENST00000623400.4	TSL:1 MANE Select	c.563T>C	p.Ile188Thr	missense	Exon 6 of 31	ENSP00000485513.1	Q9Y4E1-7
	WASHC2C	ENST00000374362.6	TSL:1	c.563T>C	p.Ile188Thr	missense	Exon 6 of 30	ENSP00000363482.2	Q9Y4E1-4
	WASHC2C	ENST00000540872.6	TSL:1	c.563T>C	p.Ile188Thr	missense	Exon 6 of 29	ENSP00000439811.1	Q9Y4E1-6

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152132 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000198 AC: 49 AN: 247032 AF XY: 0.000194

Gnomad AFR exome AF: 0.000203

Gnomad AMR exome AF: 0.000525

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000241

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000171 AC: 250 AN: 1459662 Hom.: 1 Cov.: 32 AF XY: 0.000172 AC XY: 125 AN XY: 726138

African (AFR) AF: 0.000269 AC: 9 AN: 33406

American (AMR) AF: 0.000537 AC: 24 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00266 AC: 11 AN: 4136

European-Non Finnish (NFE) AF: 0.000170 AC: 189 AN: 1111816

Other (OTH) AF: 0.000249 AC: 15 AN: 60202

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152252 Hom.: 0 Cov.: 29 AF XY: 0.000336 AC XY: 25 AN XY: 74448

African (AFR) AF: 0.000144 AC: 6 AN: 41528

American (AMR) AF: 0.00124 AC: 19 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000404

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000245 AC: 2

ExAC AF: 0.000168 AC: 20

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	0.94
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Pathogenic	0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.078	T
PhyloP100		7.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.93
MVP		0.23
ClinPred		0.78	D
GERP RS		3.7
Varity_R		0.67
gMVP		0.56
Mutation Taster		=70/30	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: rs368045657; hg19: chr10-46238872;