1-241711867-T-C

Position:

• chr1-241711867-T-C

Variant summary

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

The NM_001367482.1(WDR64):​c.1040T>C​(p.Val347Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: WDR64 NM_001367482.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

Genes affected

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

LOC124904603 (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=0.17956486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR64	NM_001367482.1	c.1040T>C	p.Val347Ala	missense_variant	9/28	ENST00000437684.7
LOC124904603	XR_007067055.1	n.189+30192A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR64	ENST00000437684.7	c.1040T>C	p.Val347Ala	missense_variant	9/28	1	NM_001367482.1	P1
WDR64	ENST00000366552.6	c.1010T>C	p.Val337Ala	missense_variant	8/27	5
WDR64	ENST00000414635.5	c.323T>C	p.Val108Ala	missense_variant	3/17	5
WDR64	ENST00000425826.3	c.1040T>C	p.Val347Ala	missense_variant, NMD_transcript_variant	9/29	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461856 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Sep 13, 2023

The c.1010T>C (p.V337A) alteration is located in exon 8 (coding exon 8) of the WDR64 gene. This alteration results from a T to C substitution at nucleotide position 1010, causing the valine (V) at amino acid position 337 to be replaced by an alanine (A). 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	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;.;.
Eigen	Benign	-0.080
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	0.90	N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.6	D;D;.
REVEL	Benign	0.063
Sift	Benign	0.12	T;T;.
Sift4G	Uncertain	0.0050	D;D;D
Vest4		0.47
MVP		0.048
MPC		0.36
ClinPred		0.90	D
GERP RS		3.7
Varity_R		0.13
gMVP		0.49

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: rs1360677347; hg19: chr1-241875169;