rs1764765191

Variant names:

• chr4-10075437-G-A
• rs1764765191
• NM_017491.5:c.1762C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-10075437-G-A
• chr4-10075437-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017491.5(WDR1):​c.1762C>T​(p.His588Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H588N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR1 NM_017491.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.06
• Publications: 0 publications found

Genes affected

WDR1 (HGNC:12754): (WD repeat domain 1) This gene encodes a protein containing 9 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, mostly including a trp-asp at the C-terminal end. WD domains are involved in protein-protein interactions. The encoded protein may help induce the disassembly of actin filaments. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18218648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR1	NM_017491.5	c.1762C>T	p.His588Tyr	missense_variant	Exon 15 of 15	ENST00000499869.7	NP_059830.1
WDR1	NM_005112.5	c.1342C>T	p.His448Tyr	missense_variant	Exon 12 of 12		NP_005103.2
WDR1	XM_017008880.3	c.1921C>T	p.His641Tyr	missense_variant	Exon 15 of 15		XP_016864369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR1	ENST00000499869.7	c.1762C>T	p.His588Tyr	missense_variant	Exon 15 of 15	5	NM_017491.5	ENSP00000427687.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	0.0070	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;.;T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	.;D;D;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.1	M;.;M;.
PhyloP100		5.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.3	N;D;N;D
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.033	D;D;D;D
Polyphen		0.34	B;P;B;P
Vest4		0.45
MutPred		0.37		Loss of glycosylation at T592 (P = 0.0398);.;Loss of glycosylation at T592 (P = 0.0398);.;
MVP		0.12
MPC		0.72
ClinPred		0.92	D
GERP RS		4.8
Varity_R		0.22
gMVP		0.43
Mutation Taster		=82/18	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: rs1764765191; hg19: chr4-10077061; COSMIC: COSV101221093; COSMIC: COSV101221093;