2-143947122-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001376312.2(GTDC1):​c.1307C>T​(p.Pro436Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,613,222 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00070 ( 8 hom. )

Consequence

GTDC1
NM_001376312.2 missense

Scores

3
16

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.17
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 Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009978741).
BP6
Variant 2-143947122-G-A is Benign according to our data. Variant chr2-143947122-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 712902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GTDC1NM_001376312.2 linkuse as main transcriptc.1307C>T p.Pro436Leu missense_variant 12/12 ENST00000682281.1 NP_001363241.1
LOC101928386NR_110237.1 linkuse as main transcriptn.721+5958G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GTDC1ENST00000682281.1 linkuse as main transcriptc.1307C>T p.Pro436Leu missense_variant 12/12 NM_001376312.2 ENSP00000507713 P1Q4AE62-1
ENST00000422799.1 linkuse as main transcriptn.715+5958G>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.000703
AC:
107
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00128
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00477
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000916
AC:
229
AN:
250012
Hom.:
3
AF XY:
0.00109
AC XY:
147
AN XY:
135260
show subpopulations
Gnomad AFR exome
AF:
0.00135
Gnomad AMR exome
AF:
0.000434
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00487
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000294
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.000701
AC:
1024
AN:
1460974
Hom.:
8
Cov.:
29
AF XY:
0.000828
AC XY:
602
AN XY:
726890
show subpopulations
Gnomad4 AFR exome
AF:
0.00164
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00445
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000409
Gnomad4 OTH exome
AF:
0.00119
GnomAD4 genome
AF:
0.000703
AC:
107
AN:
152248
Hom.:
0
Cov.:
32
AF XY:
0.00102
AC XY:
76
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.00128
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00477
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000343
Hom.:
0
Bravo
AF:
0.000688
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00111
AC:
135
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000415

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
21
DANN
Benign
0.83
DEOGEN2
Benign
0.0070
T;T;.;.;T;T;T;.
Eigen
Benign
-0.11
Eigen_PC
Benign
0.00051
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.87
.;.;D;D;D;D;.;D
M_CAP
Uncertain
0.098
D
MetaRNN
Benign
0.010
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.50
T
MutationAssessor
Benign
1.1
L;L;.;.;.;L;L;.
MutationTaster
Benign
0.98
D;D;D;D;D;N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.6
N;N;N;.;N;N;N;N
REVEL
Benign
0.12
Sift
Benign
0.28
T;T;T;.;T;T;T;T
Sift4G
Benign
0.16
T;T;T;T;T;T;T;T
Polyphen
0.99
D;D;P;.;P;D;D;.
Vest4
0.27
MVP
0.76
MPC
0.066
ClinPred
0.0098
T
GERP RS
4.1
Varity_R
0.046
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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: rs140940814; hg19: chr2-144704689; COSMIC: COSV54005164; COSMIC: COSV54005164; API