chr2-143947132-C-T

Variant summary

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

The NM_001376312.2(GTDC1):​c.1297G>A​(p.Glu433Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GTDC1
NM_001376312.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
GTDC1NM_001376312.2 linkc.1297G>A p.Glu433Lys missense_variant Exon 12 of 12 ENST00000682281.1 NP_001363241.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTDC1ENST00000682281.1 linkc.1297G>A p.Glu433Lys missense_variant Exon 12 of 12 NM_001376312.2 ENSP00000507713.1 Q4AE62-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000801
AC:
2
AN:
249794
Hom.:
1
AF XY:
0.00
AC XY:
0
AN XY:
135152
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1458864
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726042
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1297G>A (p.E433K) alteration is located in exon 12 (coding exon 9) of the GTDC1 gene. This alteration results from a G to A substitution at nucleotide position 1297, causing the glutamic acid (E) at amino acid position 433 to be replaced by a lysine (K). 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
0.11
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0095
T;T;.;.;T;T;T;.
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.87
.;.;D;D;D;D;.;D
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.14
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.6
L;L;.;.;.;L;L;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.4
N;N;N;.;N;N;N;N
REVEL
Benign
0.045
Sift
Benign
0.092
T;T;T;.;T;T;T;T
Sift4G
Benign
0.16
T;T;T;T;T;T;T;D
Polyphen
0.0080
B;B;B;.;B;B;B;.
Vest4
0.26
MutPred
0.43
Gain of MoRF binding (P = 0.003);Gain of MoRF binding (P = 0.003);.;.;.;Gain of MoRF binding (P = 0.003);Gain of MoRF binding (P = 0.003);.;
MVP
0.51
MPC
0.044
ClinPred
0.26
T
GERP RS
4.0
Varity_R
0.17
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.23
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.23
Position offset: 3

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.

Other links and lift over

dbSNP: rs763999077; hg19: chr2-144704699; API