4-176115805-C-T

Variant names:

• chr4-176115805-C-T
• rs201837131
• NM_181265.4:c.133C>T

Variant summary

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

The NM_181265.4(WDR17):​c.133C>T​(p.Arg45Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,596,410 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: WDR17 NM_181265.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

Genes affected

WDR17 (HGNC:16661): (WD repeat domain 17) This gene encodes a WD repeat-containing protein. It is abundantly expressed in retina and testis, and is thought to be a candidate gene for retinal disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181265.4. 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
	WDR17	NM_181265.4	MANE Select	c.133C>T	p.Arg45Cys	missense	Exon 3 of 29	NP_851782.3	Q8IZU2-2
	WDR17	NM_170710.5		c.205C>T	p.Arg69Cys	missense	Exon 4 of 31	NP_733828.2
	WDR17	NM_001350727.2		c.133C>T	p.Arg45Cys	missense	Exon 3 of 31	NP_001337656.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR17	ENST00000508596.6	TSL:1 MANE Select	c.133C>T	p.Arg45Cys	missense	Exon 3 of 29	ENSP00000422763.1	Q8IZU2-2
	WDR17	ENST00000280190.8	TSL:1	c.205C>T	p.Arg69Cys	missense	Exon 4 of 31	ENSP00000280190.4	Q8IZU2-1
	WDR17	ENST00000507824.6	TSL:5	c.205C>T	p.Arg69Cys	missense	Exon 3 of 30	ENSP00000422200.2	E7ESC9

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151250 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000443

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243420 AF XY: 0.00

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: 0.00000904

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1445160 Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 10 AN XY: 718340

African (AFR) AF: 0.00 AC: 0 AN: 32862

American (AMR) AF: 0.00 AC: 0 AN: 43224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25732

East Asian (EAS) AF: 0.00 AC: 0 AN: 38900

South Asian (SAS) AF: 0.00 AC: 0 AN: 82300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5454

European-Non Finnish (NFE) AF: 0.0000181 AC: 20 AN: 1104120

Other (OTH) AF: 0.00 AC: 0 AN: 59604

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151250 Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2 AN XY: 73806

African (AFR) AF: 0.00 AC: 0 AN: 41190

American (AMR) AF: 0.00 AC: 0 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67690

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.0000671 Hom.: 0

Bravo AF: 0.0000113

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	0.078
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.5
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.50
MVP		0.92
MPC		0.35
ClinPred		0.70	D
GERP RS		5.5
Varity_R		0.10
gMVP		0.26
Mutation Taster		=73/27	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

dbSNP: rs201837131; hg19: chr4-177036956;