12-120446355-C-G

Variant names:

Variant summary

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

The NM_016399.3(TRIAP1):c.18G>C(p.Glu6Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TRIAP1
NM_016399.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

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]

TRIAP1 links:

ENSG00000111780 (HGNC:):

ENSG00000111780 links:

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]

GATC links:

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
TRIAP1	NM_016399.3 link	c.18G>C	p.Glu6Asp	missense_variant	Exon 1 of 2	ENST00000546954.2	NP_057483.1	O43715
GATC	NM_176818.3 link	c.-126C>G		upstream_gene_variant		ENST00000551765.6	NP_789788.1	O43716
GATC	NR_033684.2 link	n.-89C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIAP1	ENST00000546954.2 link	c.18G>C	p.Glu6Asp	missense_variant	Exon 1 of 2	1	NM_016399.3	ENSP00000449795.1	O43715
ENSG00000111780	ENST00000551806.1 link	c.175-302C>G		intron_variant	Intron 2 of 4	3		ENSP00000450281.1	H0YIV9
GATC	ENST00000551765.6 link	c.-126C>G		upstream_gene_variant		1	NM_176818.3	ENSP00000446872.1	O43716

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.18G>C (p.E6D) alteration is located in exon 1 (coding exon 1) of the TRIAP1 gene. This alteration results from a G to C substitution at nucleotide position 18, causing the glutamic acid (E) at amino acid position 6 to be replaced by an aspartic acid (D). 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

0.23

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

Eigen

Benign

0.097

Eigen_PC

Benign

0.052

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.74

M_CAP

Benign

0.065

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.83

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.0

REVEL

Benign

0.22

Sift

Benign

0.15

Sift4G

Benign

0.28

Polyphen

0.99

Vest4

0.51

MutPred

0.51

Loss of helix (P = 0.1299);

MVP

0.093

MPC

1.3

ClinPred

0.99

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.41

gMVP

0.67

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over