2-144007185-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001376312.2(GTDC1):​c.872G>A​(p.Arg291Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000216 in 1,574,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

GTDC1
NM_001376312.2 missense

Scores

12
6
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.854

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTDC1NM_001376312.2 linkc.872G>A p.Arg291Lys 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.872G>A p.Arg291Lys missense_variant Exon 7 of 12 NM_001376312.2 ENSP00000507713.1 Q4AE62-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152080
Hom.:
0
Cov.:
32
show subpopulations
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000133
AC:
3
AN:
225504
Hom.:
0
AF XY:
0.0000166
AC XY:
2
AN XY:
120606
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:
0.0000290
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000225
AC:
32
AN:
1422018
Hom.:
0
Cov.:
28
AF XY:
0.0000156
AC XY:
11
AN XY:
703480
show subpopulations
Gnomad4 AFR exome
AF:
0.0000308
Gnomad4 AMR exome
AF:
0.0000482
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000192
Gnomad4 NFE exome
AF:
0.0000230
Gnomad4 OTH exome
AF:
0.0000510
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152080
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74300
show subpopulations
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000392
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.872G>A (p.R291K) 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 872, causing the arginine (R) at amino acid position 291 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
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.37
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.80
D;D;.;.;.;D;D;.
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.87
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
.;.;D;D;D;D;.;D
M_CAP
Uncertain
0.13
D
MetaRNN
Pathogenic
0.83
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.70
D
MutationAssessor
Pathogenic
3.4
M;M;M;.;M;M;M;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-2.4
N;N;N;.;N;N;N;N
REVEL
Pathogenic
0.69
Sift
Pathogenic
0.0
D;D;T;.;T;D;D;D
Sift4G
Pathogenic
0.0
D;D;T;D;D;D;D;D
Polyphen
1.0
D;D;D;.;.;D;D;.
Vest4
0.92
MutPred
0.69
Gain of methylation at R291 (P = 0.0037);Gain of methylation at R291 (P = 0.0037);Gain of methylation at R291 (P = 0.0037);.;Gain of methylation at R291 (P = 0.0037);Gain of methylation at R291 (P = 0.0037);Gain of methylation at R291 (P = 0.0037);.;
MVP
0.75
MPC
0.28
ClinPred
0.86
D
GERP RS
5.7
Varity_R
0.73
gMVP
0.79

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: rs780580259; hg19: chr2-144764752; API