1-108971494-T-A

Position:

• chr1-108971494-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142551.2(WDR47):​c.2696A>T​(p.Gln899Leu) 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. 14/21 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: 3.19

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33518204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR47	NM_001142551.2	c.2696A>T	p.Gln899Leu	missense_variant	15/15	ENST00000369962.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR47	ENST00000369962.8	c.2696A>T	p.Gln899Leu	missense_variant	15/15	1	NM_001142551.2	A1
WDR47	ENST00000400794.7	c.2720A>T	p.Gln907Leu	missense_variant	15/15	1
WDR47	ENST00000369965.8	c.2699A>T	p.Gln900Leu	missense_variant	15/15	1		P5
WDR47	ENST00000361054.7	c.2612A>T	p.Gln871Leu	missense_variant	14/14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 17, 2024

The c.2720A>T (p.Q907L) alteration is located in exon 15 (coding exon 14) of the WDR47 gene. This alteration results from a A to T substitution at nucleotide position 2720, causing the glutamine (Q) at amino acid position 907 to be replaced by a leucine (L). 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	0.18
BayesDel_addAF	Benign	0.0020	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.094	.;T;.;.;T
Eigen	Benign	-0.0057
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.34	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	.;N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.5	N;N;N;N;.
REVEL	Benign	0.16
Sift	Benign	0.23	T;T;T;T;.
Sift4G	Benign	0.61	T;T;T;T;T
Polyphen		0.081, 0.0030, 0.0060	.;B;B;B;.
Vest4		0.53
MutPred		0.55		.;Loss of solvent accessibility (P = 0.0468);.;.;.;
MVP		0.18
MPC		0.98
ClinPred		0.63	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.11

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: chr1-109514116;