4-176125301-T-C

Position:

• chr4-176125301-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181265.4(WDR17):​c.736T>C​(p.Ser246Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR17 NM_181265.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.15

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR17	NM_181265.4	c.736T>C	p.Ser246Pro	missense_variant	5/29	ENST00000508596.6	NP_851782.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR17	ENST00000508596.6	c.736T>C	p.Ser246Pro	missense_variant	5/29	1	NM_181265.4	ENSP00000422763.1
WDR17	ENST00000280190.8	c.808T>C	p.Ser270Pro	missense_variant	6/31	1		ENSP00000280190.4
WDR17	ENST00000507824.6	c.757T>C	p.Ser253Pro	missense_variant	5/30	5		ENSP00000422200.2
WDR17	ENST00000505894.2	c.229+5204T>C		intron_variant		5		ENSP00000426847.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.808T>C (p.S270P) alteration is located in exon 6 (coding exon 5) of the WDR17 gene. This alteration results from a T to C substitution at nucleotide position 808, causing the serine (S) at amino acid position 270 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	.;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.050	D;D;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		0.97	.;D;.
Vest4		0.52
MutPred		0.55		.;Gain of sheet (P = 0.0827);.;
MVP		0.93
MPC		0.41
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.45
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-177046452;