2-144007245-C-T

Position:

• chr2-144007245-C-T

Variant summary

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

The NM_001376312.2(GTDC1):​c.812G>A​(p.Cys271Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTDC1 NM_001376312.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.823

Genes affected

GTDC1 (HGNC:20887): (glycosyltransferase like domain containing 1) Predicted to enable glycosyltransferase activity. [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=0.08995727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTDC1	NM_001376312.2	c.812G>A	p.Cys271Tyr	missense_variant	7/12	ENST00000682281.1	NP_001363241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTDC1	ENST00000682281.1	c.812G>A	p.Cys271Tyr	missense_variant	7/12		NM_001376312.2	ENSP00000507713	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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, 2022

The c.812G>A (p.C271Y) alteration is located in exon 7 (coding exon 4) of the GTDC1 gene. This alteration results from a G to A substitution at nucleotide position 812, causing the cysteine (C) at amino acid position 271 to be replaced by a tyrosine (Y). 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	0.082
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.3
DANN	Benign	0.21
DEOGEN2	Benign	0.019	T;T;.;.;.;T;T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.74	.;.;T;T;T;T;.;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.090	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L;L;L;.;L;L;L;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.78	N;N;N;.;N;N;N;N
REVEL	Benign	0.083
Sift	Benign	0.46	T;T;T;.;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;.;B;B;.
Vest4		0.18
MutPred		0.48		Loss of catalytic residue at P270 (P = 0.0094);Loss of catalytic residue at P270 (P = 0.0094);Loss of catalytic residue at P270 (P = 0.0094);.;Loss of catalytic residue at P270 (P = 0.0094);Loss of catalytic residue at P270 (P = 0.0094);Loss of catalytic residue at P270 (P = 0.0094);.;
MVP		0.28
MPC		0.075
ClinPred		0.073	T
GERP RS		2.2
Varity_R		0.10
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs1345731321; hg19: chr2-144764812;