1-241652598-T-G

Position:

• chr1-241652598-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367482.1(WDR64):​c.114T>G​(p.Asp38Glu) 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 NM_001367482.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.529

Genes affected

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

OPN3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046492487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR64	NM_001367482.1	c.114T>G	p.Asp38Glu	missense_variant	1/28	ENST00000437684.7	NP_001354411.1
WDR64	XM_011544087.3	c.114T>G	p.Asp38Glu	missense_variant	1/23		XP_011542389.1
WDR64	XM_011544091.2	c.114T>G	p.Asp38Glu	missense_variant	1/20		XP_011542393.1
WDR64	XM_011544092.3	c.114T>G	p.Asp38Glu	missense_variant	1/19		XP_011542394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR64	ENST00000437684.7	c.114T>G	p.Asp38Glu	missense_variant	1/28	1	NM_001367482.1	ENSP00000402446.4
WDR64	ENST00000366552.6	c.114T>G	p.Asp38Glu	missense_variant	1/27	5		ENSP00000355510.2
WDR64	ENST00000425826.3	n.114T>G		non_coding_transcript_exon_variant	1/29	2		ENSP00000406342.3
OPN3	ENST00000463155.5	n.74+24705A>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Apr 29, 2024

The c.114T>G (p.D38E) alteration is located in exon 1 (coding exon 1) of the WDR64 gene. This alteration results from a T to G substitution at nucleotide position 114, causing the aspartic acid (D) at amino acid position 38 to be replaced by a glutamic acid (E). 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	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00073	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.13
Sift	Benign	0.69	T
Sift4G	Benign	0.89	T
Vest4		0.041
MutPred		0.18		Gain of loop (P = 0.1069);
MVP		0.040
MPC		0.069
ClinPred		0.10	T
GERP RS		-6.2
Varity_R		0.041
gMVP		0.054

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-241815900;