1-109002332-T-C

Position:

• chr1-109002332-T-C

Variant summary

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

The NM_001142551.2(WDR47):​c.1325A>G​(p.Gln442Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,906 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WDR47 NM_001142551.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.15

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR47	NM_001142551.2	c.1325A>G	p.Gln442Arg	missense_variant	7/15	ENST00000369962.8	NP_001136023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR47	ENST00000369962.8	c.1325A>G	p.Gln442Arg	missense_variant	7/15	1	NM_001142551.2	ENSP00000358979	A1
WDR47	ENST00000400794.7	c.1349A>G	p.Gln450Arg	missense_variant	7/15	1		ENSP00000383599
WDR47	ENST00000369965.8	c.1328A>G	p.Gln443Arg	missense_variant	7/15	1		ENSP00000358982	P5
WDR47	ENST00000361054.7	c.1241A>G	p.Gln414Arg	missense_variant	6/14	5		ENSP00000354339

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460906 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726770

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

Jun 07, 2023

The c.1349A>G (p.Q450R) alteration is located in exon 7 (coding exon 6) of the WDR47 gene. This alteration results from a A to G substitution at nucleotide position 1349, causing the glutamine (Q) at amino acid position 450 to be replaced by an arginine (R). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	.;T;.;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.50	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.1	.;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.036	D;D;D;D;D
Polyphen		0.99, 0.98	.;D;D;D;.
Vest4		0.68
MutPred		0.25		.;Loss of helix (P = 0.0033);.;.;.;
MVP		0.23
MPC		0.85
ClinPred		0.94	D
GERP RS		5.1
Varity_R		0.49
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-109544954;