chr1-241652518-G-A

Position:

• chr1-241652518-G-A

Variant summary

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

The ENST00000437684.7(WDR64):​c.34G>A​(p.Ala12Thr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR64 ENST00000437684.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.216

Genes affected

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

OPN3 (HGNC:):

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=0.09913644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR64	NM_001367482.1	c.34G>A	p.Ala12Thr	missense_variant	1/28	ENST00000437684.7	NP_001354411.1
WDR64	XM_011544087.3	c.34G>A	p.Ala12Thr	missense_variant	1/23		XP_011542389.1
WDR64	XM_011544091.2	c.34G>A	p.Ala12Thr	missense_variant	1/20		XP_011542393.1
WDR64	XM_011544092.3	c.34G>A	p.Ala12Thr	missense_variant	1/19		XP_011542394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR64	ENST00000437684.7	c.34G>A	p.Ala12Thr	missense_variant	1/28	1	NM_001367482.1	ENSP00000402446.4
WDR64	ENST00000366552.6	c.34G>A	p.Ala12Thr	missense_variant	1/27	5		ENSP00000355510.2
WDR64	ENST00000425826.3	n.34G>A		non_coding_transcript_exon_variant	1/29	2		ENSP00000406342.3
OPN3	ENST00000463155.5	n.74+24785C>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Jan 20, 2023

The c.34G>A (p.A12T) alteration is located in exon 1 (coding exon 1) of the WDR64 gene. This alteration results from a G to A substitution at nucleotide position 34, causing the alanine (A) at amino acid position 12 to be replaced by a threonine (T). 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	0.080
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.054
Sift	Benign	0.24	T
Sift4G	Benign	0.14	T
Vest4		0.039
MutPred		0.14		Loss of ubiquitination at K7 (P = 0.0896);
MVP		0.040
MPC		0.071
ClinPred		0.065	T
GERP RS		-0.20
Varity_R		0.029
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs1665399604; hg19: chr1-241815820;