Variant chr11-118659902-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007180.3(TREH):c.1165A>G(p.Thr389Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,551,634 control chromosomes in the GnomAD database, including 42,148 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3328 hom., cov: 32)

Exomes 𝑓: 0.23 ( 38820 hom. )

Consequence

TREH
NM_007180.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.897

Variant links:

Genes affected

TREH (HGNC:12266): (trehalase) This gene encodes an enzyme that hydrolyses trehalose, a disaccharide formed from two glucose molecules found mainly in fungi, plants, and insects. A partial duplication of this gene is located adjacent to this locus on chromosome 11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

TREH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010524929).

BP6

Variant 11-118659902-T-C is Benign according to our data. Variant chr11-118659902-T-C is described in ClinVar as [Benign]. Clinvar id is 3060563.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREH	NM_007180.3 linkuse as main transcript	c.1165A>G	p.Thr389Ala	missense_variant	11/15	ENST00000264029.9
TREH	NM_001301065.2 linkuse as main transcript	c.1072A>G	p.Thr358Ala	missense_variant	10/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREH	ENST00000264029.9 linkuse as main transcript	c.1165A>G	p.Thr389Ala	missense_variant	11/15	1	NM_007180.3	P1	O43280-1
TREH	ENST00000397925.2 linkuse as main transcript	c.1072A>G	p.Thr358Ala	missense_variant	10/14	1			O43280-2
TREH	ENST00000531295.5 linkuse as main transcript	n.1428A>G		non_coding_transcript_exon_variant	10/10	5
TREH	ENST00000613915.4 linkuse as main transcript	c.*942A>G		3_prime_UTR_variant, NMD_transcript_variant	9/13	2

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30699

AN:

152062

Hom.:

3326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.195

GnomAD3 exomes

AF:

0.235

AC:

36939

AN:

157018

Hom.:

4686

AF XY:

0.245

AC XY:

20358

AN XY:

83030

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.251

Gnomad SAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.232

AC:

324371

AN:

1399454

Hom.:

38820

Cov.:

AF XY:

0.236

AC XY:

162566

AN XY:

690246

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.203

Gnomad4 EAS exome

AF:

0.220

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.202

AC:

30709

AN:

152180

Hom.:

3328

Cov.:

AF XY:

0.205

AC XY:

15268

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.218

Hom.:

1446

Bravo

AF:

0.193

TwinsUK

AF:

0.217

AC:

806

ALSPAC

AF:

0.221

AC:

850

ESP6500AA

AF:

0.103

AC:

379

ESP6500EA

AF:

0.193

AC:

1504

ExAC

AF:

0.145

AC:

9461

Asia WGS

AF:

0.269

AC:

935

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TREH-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.36

DANN

Benign

0.38

DEOGEN2

Benign

0.030

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00039

LIST_S2

Benign

0.087

T;T

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.098

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.0020

MPC

0.030

ClinPred

0.0019

GERP RS

3.8

Varity_R

0.047

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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