1-108983401-T-G

Position:

• chr1-108983401-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_001142551.2(WDR47):​c.1976A>C​(p.His659Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR47 NM_001142551.2 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.67

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823
• PP5: Variant 1-108983401-T-G is Pathogenic according to our data. Variant chr1-108983401-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2673280.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR47	NM_001142551.2	c.1976A>C	p.His659Pro	missense_variant	11/15	ENST00000369962.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR47	ENST00000369962.8	c.1976A>C	p.His659Pro	missense_variant	11/15	1	NM_001142551.2	A1
WDR47	ENST00000400794.7	c.2000A>C	p.His667Pro	missense_variant	11/15	1
WDR47	ENST00000369965.8	c.1979A>C	p.His660Pro	missense_variant	11/15	1		P5
WDR47	ENST00000361054.7	c.1892A>C	p.His631Pro	missense_variant	10/14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Mendelics

Dec 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T;.;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.73	.;N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-7.0	D;D;D;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D
Polyphen		1.0, 1.0, 1.0	.;D;D;D;.
Vest4		0.84
MutPred		0.62		.;Gain of methylation at K661 (P = 0.0677);.;.;.;
MVP		0.37
MPC		2.5
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.90
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-109526023;