12-120446333-C-T

Variant summary

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

The NM_016399.3(TRIAP1):​c.40G>A​(p.Glu14Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,614,136 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: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TRIAP1
NM_016399.3 missense

Scores

2
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.16
Variant links:
Genes affected
TRIAP1 (HGNC:26937): (TP53 regulated inhibitor of apoptosis 1) Enables p53 binding activity. Contributes to phosphatidic acid transfer activity. Involved in several processes, including DNA damage response, signal transduction by p53 class mediator; negative regulation of apoptotic process; and positive regulation of phospholipid transport. Located in mitochondrial intermembrane space and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]
GATC (HGNC:25068): (glutamyl-tRNA amidotransferase subunit C) Enables glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity. Involved in glutaminyl-tRNAGln biosynthesis via transamidation and mitochondrial translation. Located in mitochondrion. Part of glutamyl-tRNA(Gln) amidotransferase complex. Implicated in combined oxidative phosphorylation deficiency 42. [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=0.21968463).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIAP1NM_016399.3 linkc.40G>A p.Glu14Lys missense_variant Exon 1 of 2 ENST00000546954.2 NP_057483.1 O43715
GATCNM_176818.3 linkc.-148C>T upstream_gene_variant ENST00000551765.6 NP_789788.1 O43716
GATCNR_033684.2 linkn.-111C>T upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIAP1ENST00000546954.2 linkc.40G>A p.Glu14Lys missense_variant Exon 1 of 2 1 NM_016399.3 ENSP00000449795.1 O43715
ENSG00000111780ENST00000551806.1 linkc.175-324C>T intron_variant Intron 2 of 4 3 ENSP00000450281.1 H0YIV9
GATCENST00000551765.6 linkc.-148C>T upstream_gene_variant 1 NM_176818.3 ENSP00000446872.1 O43716

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152250
Hom.:
0
Cov.:
33
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:
0.000769
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:
0.0000438
AC:
11
AN:
251426
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000544
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:
0.00000889
AC:
13
AN:
1461886
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000302
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152250
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000769
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 30, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.40G>A (p.E14K) alteration is located in exon 1 (coding exon 1) of the TRIAP1 gene. This alteration results from a G to A substitution at nucleotide position 40, causing the glutamic acid (E) at amino acid position 14 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
0.67
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
T
Eigen
Benign
0.077
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Benign
0.58
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.066
D
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-1.1
T
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.14
Sift
Benign
0.26
T
Sift4G
Benign
0.49
T
Polyphen
0.033
B
Vest4
0.70
MutPred
0.42
Gain of methylation at E14 (P = 0.0047);
MVP
0.22
MPC
0.66
ClinPred
0.50
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.78
gMVP
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs368215298; hg19: chr12-120884136; API