Variant 3-108853647-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016388.4(TRAT1):c.331G>A(p.Ala111Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

TRAT1
NM_016388.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57

Variant links:

Genes affected

TRAT1 (HGNC:30698): (T cell receptor associated transmembrane adaptor 1) Predicted to enable transmembrane receptor protein tyrosine kinase adaptor activity. Acts upstream of or within negative regulation of receptor recycling; negative regulation of transport; and positive regulation of signal transduction. Located in centriolar satellite; mitotic spindle; and plasma membrane. Part of T cell receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

TRAT1 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	Protein	UniProt
TRAT1	NM_016388.4 linkuse as main transcript	c.331G>A	p.Ala111Thr	missense_variant	6/6	ENST00000295756.11	NP_057472.2
TRAT1	NM_001317747.2 linkuse as main transcript	c.220G>A	p.Ala74Thr	missense_variant	5/5		NP_001304676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAT1	ENST00000295756.11 linkuse as main transcript	c.331G>A	p.Ala111Thr	missense_variant	6/6	1	NM_016388.4	ENSP00000295756	P1
TRAT1	ENST00000426646.1 linkuse as main transcript	c.220G>A	p.Ala74Thr	missense_variant	5/5	1		ENSP00000410097

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251004

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000294

AC:

430

AN:

1461740

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

206

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000310

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000236

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

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

May 02, 2024

The c.331G>A (p.A111T) alteration is located in exon 6 (coding exon 6) of the TRAT1 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the alanine (A) at amino acid position 111 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;T

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.96

N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.93

P;P

Vest4

0.62

MVP

0.62

MPC

0.23

ClinPred

0.064

GERP RS

2.9

Varity_R

0.24

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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