Variant 8-92892021-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001171797.2(TRIQK):c.115G>A(p.Ala39Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000101 in 1,381,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TRIQK
NM_001171797.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

Variant links:

Genes affected

TRIQK (HGNC:27828): (triple QxxK/R motif containing) Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRIQK links:

(HGNC:):

links:

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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/exons	MANE	UniProt
TRIQK	NM_001171797.2 linkuse as main transcript	c.115G>A	p.Ala39Thr	missense_variant	4/5	ENST00000521988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIQK	ENST00000521988.6 linkuse as main transcript	c.115G>A	p.Ala39Thr	missense_variant	4/5	1	NM_001171797.2	P1
	ENST00000523197.5 linkuse as main transcript	n.124+5078C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1381448

Hom.:

Cov.:

AF XY:

0.00000587

AC XY:

AN XY:

681710

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:

0.0000130

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2024

The c.115G>A (p.A39T) alteration is located in exon 5 (coding exon 2) of the TRIQK gene. This alteration results from a G to A substitution at nucleotide position 115, causing the alanine (A) at amino acid position 39 to be replaced by a threonine (T). 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

0.82

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T;T;T;T;T;T;T;T;T;T;T;T;.;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

.;D;.;.;.;.;.;.;.;.;D;.;.;D;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.54

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.084

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;.

Polyphen

1.0

D;D;D;.;D;D;.;D;.;D;.;D;D;.;.

Vest4

0.72

MutPred

0.21

Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);

MVP

0.12

ClinPred

1.0

GERP RS

5.8

Varity_R

0.71

gMVP

0.42

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