chr4-176096556-C-A

Position:

• chr4-176096556-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170710.5(WDR17):​c.37C>A​(p.Gln13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR17 NM_170710.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13488984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR17	NM_181265.4	c.-6-15019C>A		intron_variant		ENST00000508596.6	NP_851782.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR17	ENST00000508596.6	c.-6-15019C>A		intron_variant		1	NM_181265.4	ENSP00000422763.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Jul 15, 2024

The c.37C>A (p.Q13K) alteration is located in exon 2 (coding exon 1) of the WDR17 gene. This alteration results from a C to A substitution at nucleotide position 37, causing the glutamine (Q) at amino acid position 13 to be replaced by a lysine (K). 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	0.081
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0089	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.0	N;N
REVEL	Benign	0.11
Sift	Benign	0.14	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.043	B;.
Vest4		0.40
MutPred		0.41		Gain of ubiquitination at Q13 (P = 0.0162);Gain of ubiquitination at Q13 (P = 0.0162);
MVP		0.68
MPC		0.55
ClinPred		0.62	D
GERP RS		4.8
Varity_R		0.063
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr4-177017707;