chr2-144007255-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001376312.2(GTDC1):​c.802G>T​(p.Val268Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 1,460,790 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GTDC1
NM_001376312.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.818
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08858025).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTDC1NM_001376312.2 linkc.802G>T p.Val268Phe missense_variant Exon 7 of 12 ENST00000682281.1 NP_001363241.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTDC1ENST00000682281.1 linkc.802G>T p.Val268Phe missense_variant Exon 7 of 12 NM_001376312.2 ENSP00000507713.1 Q4AE62-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152114
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249988
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135118
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000315
AC:
46
AN:
1460790
Hom.:
0
Cov.:
31
AF XY:
0.0000330
AC XY:
24
AN XY:
726704
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:
0.0000405
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74310
Gnomad4 AFR
AF:
0.00
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.802G>T (p.V268F) alteration is located in exon 7 (coding exon 4) of the GTDC1 gene. This alteration results from a G to T substitution at nucleotide position 802, causing the valine (V) at amino acid position 268 to be replaced by a phenylalanine (F). 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
0.070
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
1.1
DANN
Benign
0.35
DEOGEN2
Benign
0.0045
T;T;.;.;.;T;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.64
.;.;T;T;T;T;.;T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.089
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.13
N;N;N;.;N;N;N;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.39
N;N;N;.;N;N;N;N
REVEL
Benign
0.034
Sift
Benign
0.34
T;T;T;.;T;T;T;T
Sift4G
Benign
0.82
T;T;T;T;T;T;T;T
Polyphen
0.0
B;B;B;.;.;B;B;.
Vest4
0.11
MutPred
0.54
Loss of glycosylation at T267 (P = 0.1007);Loss of glycosylation at T267 (P = 0.1007);Loss of glycosylation at T267 (P = 0.1007);.;Loss of glycosylation at T267 (P = 0.1007);Loss of glycosylation at T267 (P = 0.1007);Loss of glycosylation at T267 (P = 0.1007);.;
MVP
0.20
MPC
0.046
ClinPred
0.030
T
GERP RS
-1.3
Varity_R
0.054
gMVP
0.19

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

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

Other links and lift over

dbSNP: rs766181926; hg19: chr2-144764822; API