rs201294651

Variant names:

• chr4-176120035-C-T
• rs201294651
• NM_181265.4:c.476C>T

Variant summary

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

The NM_181265.4(WDR17):​c.476C>T​(p.Thr159Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: WDR17 NM_181265.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3118071).

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.476C>T	p.Thr159Ile	missense	Exon 4 of 29	NP_851782.3	Q8IZU2-2
	WDR17	NM_170710.5		c.548C>T	p.Thr183Ile	missense	Exon 5 of 31	NP_733828.2
	WDR17	NM_001350727.2		c.476C>T	p.Thr159Ile	missense	Exon 4 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.476C>T	p.Thr159Ile	missense	Exon 4 of 29	ENSP00000422763.1	Q8IZU2-2
	WDR17	ENST00000280190.8	TSL:1	c.548C>T	p.Thr183Ile	missense	Exon 5 of 31	ENSP00000280190.4	Q8IZU2-1
	WDR17	ENST00000507824.6	TSL:5	c.548C>T	p.Thr183Ile	missense	Exon 4 of 30	ENSP00000422200.2	E7ESC9

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152022 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251422 AF XY: 0.0000147

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74392

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

African (AFR) AF: 0.00 AC: 0 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2116

⚠️ 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.

ExAC AF: 0.0000165 AC: 2

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	0.095
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.17
Sift	Benign	0.41	T
Sift4G	Benign	0.29	T
Polyphen		0.21	B
Vest4		0.53
MutPred		0.54		Gain of methylation at K186 (P = 0.0547)
MVP		0.87
MPC		0.15
ClinPred		0.16	T
GERP RS		5.4
PromoterAI		-0.018	Neutral
Varity_R		0.14
gMVP		0.34
Mutation Taster		=73/27	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: rs201294651; hg19: chr4-177041186;