Genetic Variant TRIAP1:p.Glu73Lys (chr12-120444886-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016399.3(TRIAP1):c.217G>A(p.Glu73Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000638 in 1,613,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

TRIAP1
NM_016399.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018847287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIAP1	NM_016399.3 link	c.217G>A	p.Glu73Lys	missense_variant	Exon 2 of 2	ENST00000546954.2	NP_057483.1	O43715

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIAP1	ENST00000546954.2 link	c.217G>A	p.Glu73Lys	missense_variant	Exon 2 of 2	1	NM_016399.3	ENSP00000449795.1	O43715
ENSG00000111780	ENST00000551806.1 link	c.175-1771C>T		intron_variant	Intron 2 of 4	3		ENSP00000450281.1	H0YIV9
TRIAP1	ENST00000302432.3 link	n.475G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00288

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:

0.000124

AC:

AN:

250990

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.0000623

AC:

AN:

1461258

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00222

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00288

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:

0.000148

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.217G>A (p.E73K) alteration is located in exon 2 (coding exon 2) of the TRIAP1 gene. This alteration results from a G to A substitution at nucleotide position 217, causing the glutamic acid (E) at amino acid position 73 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

Benign

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Benign

-0.057

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.74

M_CAP

Benign

0.013

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.59

REVEL

Benign

0.062

Sift

Benign

0.26

Sift4G

Benign

0.52

Polyphen

0.18

Vest4

0.13

MVP

0.14

MPC

0.64

ClinPred

0.34

GERP RS

4.9

Varity_R

0.20

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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