1-241687565-T-G

Position:

• chr1-241687565-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000437684.7(WDR64):​c.944T>G​(p.Leu315Trp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR64 ENST00000437684.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17

Genes affected

WDR64 (HGNC:26570): (WD repeat domain 64)

LOC124904603 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3677603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR64	NM_001367482.1	c.944T>G	p.Leu315Trp	missense_variant	8/28	ENST00000437684.7	NP_001354411.1
LOC124904603	XR_007067055.1	n.190-10065A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR64	ENST00000437684.7	c.944T>G	p.Leu315Trp	missense_variant	8/28	1	NM_001367482.1	ENSP00000402446	P1
WDR64	ENST00000366552.6	c.914T>G	p.Leu305Trp	missense_variant	7/27	5		ENSP00000355510
WDR64	ENST00000414635.5	c.227T>G	p.Leu76Trp	missense_variant	2/17	5		ENSP00000406656
WDR64	ENST00000425826.3	c.944T>G	p.Leu315Trp	missense_variant, NMD_transcript_variant	8/29	2		ENSP00000406342

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

Nov 18, 2023

The c.914T>G (p.L305W) alteration is located in exon 7 (coding exon 7) of the WDR64 gene. This alteration results from a T to G substitution at nucleotide position 914, causing the leucine (L) at amino acid position 305 to be replaced by a tryptophan (W). 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	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.086	T;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.5	M;.;.
MutationTaster	Benign	0.88	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.8	D;D;.
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.77
MutPred		0.40		Loss of disorder (P = 0.0655);.;.;
MVP		0.33
MPC		0.51
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.54
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr1-241850867;