Variant 2-143947126-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001376312.2(GTDC1):c.1303G>A(p.Ala435Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,612,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

GTDC1
NM_001376312.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.149

Variant links:

Genes affected

GTDC1 (HGNC:20887): (glycosyltransferase like domain containing 1) Predicted to enable glycosyltransferase activity. [provided by Alliance of Genome Resources, Apr 2022]

GTDC1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06711766).

BP6

Variant 2-143947126-C-T is Benign according to our data. Variant chr2-143947126-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3283035.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTDC1	NM_001376312.2 linkuse as main transcript	c.1303G>A	p.Ala435Thr	missense_variant	12/12	ENST00000682281.1	NP_001363241.1
LOC101928386	NR_110237.1 linkuse as main transcript	n.721+5962C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTDC1	ENST00000682281.1 linkuse as main transcript	c.1303G>A	p.Ala435Thr	missense_variant	12/12		NM_001376312.2	ENSP00000507713	P1	Q4AE62-1
	ENST00000422799.1 linkuse as main transcript	n.715+5962C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

249840

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1460020

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726518

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.3

DANN

Benign

0.82

DEOGEN2

Benign

0.0051

T;T;.;.;T;T;T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.68

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.59

.;.;T;T;T;T;.;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.067

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

N;N;.;.;.;N;N;.

MutationTaster

Benign

0.92

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.42

N;N;N;.;N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.50

T;T;T;.;T;T;T;T

Sift4G

Benign

0.46

T;T;T;T;T;T;T;T

Polyphen

0.021

B;B;B;.;B;B;B;.

Vest4

0.058

MutPred

0.39

Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);.;.;.;Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);.;

MVP

0.40

MPC

0.038

ClinPred

0.037

GERP RS

0.47

Varity_R

0.032

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over