1-108995664-G-A

Position:

• chr1-108995664-G-A

Variant summary

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

The NM_001142551.2(WDR47):​c.1607C>T​(p.Ser536Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR47 NM_001142551.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53

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=0.09731227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR47	NM_001142551.2	c.1607C>T	p.Ser536Leu	missense_variant	8/15	ENST00000369962.8	NP_001136023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR47	ENST00000369962.8	c.1607C>T	p.Ser536Leu	missense_variant	8/15	1	NM_001142551.2	ENSP00000358979.3
WDR47	ENST00000400794.7	c.1631C>T	p.Ser544Leu	missense_variant	8/15	1		ENSP00000383599.3
WDR47	ENST00000369965.8	c.1610C>T	p.Ser537Leu	missense_variant	8/15	1		ENSP00000358982.4
WDR47	ENST00000361054.7	c.1523C>T	p.Ser508Leu	missense_variant	7/14	5		ENSP00000354339.3

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

Aug 19, 2024

The c.1631C>T (p.S544L) alteration is located in exon 8 (coding exon 7) of the WDR47 gene. This alteration results from a C to T substitution at nucleotide position 1631, causing the serine (S) at amino acid position 544 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	0.072
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	.;T;.;.;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.097	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.68	N;N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.28	T;T;T;T;T
Sift4G	Benign	0.80	T;T;T;T;T
Polyphen		0.020, 0.034, 0.0080	.;B;B;B;.
Vest4		0.23
MutPred		0.24		.;Loss of glycosylation at S536 (P = 0.0357);.;.;.;
MVP		0.082
MPC		0.043
ClinPred		0.21	T
GERP RS		4.6
Varity_R		0.060
gMVP		0.27

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: chr1-109538286;