1-108991277-G-C

Position:

• chr1-108991277-G-C

Variant summary

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

The NM_001142551.2(WDR47):​c.1744C>G​(p.Leu582Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR47 NM_001142551.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

Genes affected

WDR47 (HGNC:29141): (WD repeat domain 47) Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07796422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR47	NM_001142551.2	c.1744C>G	p.Leu582Val	missense_variant	9/15	ENST00000369962.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR47	ENST00000369962.8	c.1744C>G	p.Leu582Val	missense_variant	9/15	1	NM_001142551.2	A1
WDR47	ENST00000400794.7	c.1768C>G	p.Leu590Val	missense_variant	9/15	1
WDR47	ENST00000369965.8	c.1747C>G	p.Leu583Val	missense_variant	9/15	1		P5
WDR47	ENST00000361054.7	c.1660C>G	p.Leu554Val	missense_variant	8/14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460858 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726686

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Dec 27, 2023

The c.1768C>G (p.L590V) alteration is located in exon 9 (coding exon 8) of the WDR47 gene. This alteration results from a C to G substitution at nucleotide position 1768, causing the leucine (L) at amino acid position 590 to be replaced by a valine (V). 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	0.064
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	.;T;.;.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.75	T;T;T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.078	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	.;L;.;.;.
MutationTaster	Benign	0.76	N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.14	N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.077	T;T;D;D;D
Sift4G	Benign	0.26	T;T;T;T;T
Polyphen		0.50, 0.37, 0.24	.;P;B;B;.
Vest4		0.15
MutPred		0.27		.;Loss of sheet (P = 0.0054);.;.;.;
MVP		0.36
MPC		0.046
ClinPred		0.15	T
GERP RS		3.5
Varity_R		0.078
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1425358889; hg19: chr1-109533899;