1-109002273-C-G

Position:

• chr1-109002273-C-G

Variant summary

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

The NM_001142551.2(WDR47):​c.1384G>C​(p.Glu462Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: WDR47 NM_001142551.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22

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=0.11143994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR47	NM_001142551.2	c.1384G>C	p.Glu462Gln	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.1384G>C	p.Glu462Gln	missense_variant	7/15	1	NM_001142551.2	ENSP00000358979	A1
WDR47	ENST00000400794.7	c.1408G>C	p.Glu470Gln	missense_variant	7/15	1		ENSP00000383599
WDR47	ENST00000369965.8	c.1387G>C	p.Glu463Gln	missense_variant	7/15	1		ENSP00000358982	P5
WDR47	ENST00000361054.7	c.1300G>C	p.Glu434Gln	missense_variant	6/14	5		ENSP00000354339

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 05, 2021

The c.1408G>C (p.E470Q) alteration is located in exon 7 (coding exon 6) of the WDR47 gene. This alteration results from a G to C substitution at nucleotide position 1408, causing the glutamic acid (E) at amino acid position 470 to be replaced by a glutamine (Q). 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	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	.;T;.;.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.027
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	.;N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.16	N;N;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.24	T;T;T;T;T
Sift4G	Benign	0.60	T;T;T;T;T
Polyphen		0.0050, 0.0030, 0.0040	.;B;B;B;.
Vest4		0.20
MutPred		0.33		.;Gain of sheet (P = 0.0344);.;.;.;
MVP		0.17
MPC		0.57
ClinPred		0.77	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.16

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: chr1-109544895;