chr1-27263159-G-T

Position:

• chr1-27263159-G-T

Variant summary

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

The NM_001276252.2(WDTC1):​c.56G>T​(p.Gly19Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDTC1 NM_001276252.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.19

Genes affected

WDTC1 (HGNC:29175): (WD and tetratricopeptide repeats 1) Predicted to enable enzyme inhibitor activity; histone binding activity; and histone deacetylase binding activity. Predicted to be involved in negative regulation of fatty acid biosynthetic process. Predicted to act upstream of or within several processes, including cellular response to insulin stimulus; glucose metabolic process; and negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of Cul4-RING E3 ubiquitin ligase complex. Predicted to be active in cytoplasm. [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	UniProt
WDTC1	NM_001276252.2	c.56G>T	p.Gly19Val	missense_variant	3/16	ENST00000319394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDTC1	ENST00000319394.8	c.56G>T	p.Gly19Val	missense_variant	3/16	1	NM_001276252.2	P5
WDTC1	ENST00000361771.7	c.56G>T	p.Gly19Val	missense_variant	3/16	1		A1
WDTC1	ENST00000447062.2	c.56G>T	p.Gly19Val	missense_variant, NMD_transcript_variant	2/16	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Apr 19, 2024

The c.56G>T (p.G19V) alteration is located in exon 3 (coding exon 2) of the WDTC1 gene. This alteration results from a G to T substitution at nucleotide position 56, causing the glycine (G) at amino acid position 19 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Benign	0.42
DEOGEN2	Benign	0.079	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0060	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	1.1	N;N
REVEL	Benign	0.25
Sift	Benign	0.31	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.0010	B;B
Vest4		0.81
MutPred		0.45		Loss of disorder (P = 0.0509);Loss of disorder (P = 0.0509);
MVP		0.49
MPC		1.1
ClinPred		0.62	D
GERP RS		5.7
Varity_R		0.18
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2012537022; hg19: chr1-27589650;