11-118658993-C-T

Position:

chr11-118658993-C-T

Variant summary

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

The ENST00000264029.9(TREH):c.1457G>A(p.Arg486Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,613,674 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R486W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

TREH
ENST00000264029.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.111

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 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
TREH	NM_007180.3 linkuse as main transcript	c.1457G>A	p.Arg486Gln	missense_variant	13/15	ENST00000264029.9	NP_009111.2	O43280-1
TREH	NM_001301065.2 linkuse as main transcript	c.1364G>A	p.Arg455Gln	missense_variant	12/14		NP_001287994.1	O43280-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TREH	ENST00000264029.9 linkuse as main transcript	c.1457G>A	p.Arg486Gln	missense_variant	13/15	1	NM_007180.3	ENSP00000264029.5	O43280-1
TREH	ENST00000397925.2 linkuse as main transcript	c.1364G>A	p.Arg455Gln	missense_variant	12/14	1		ENSP00000381020.2	O43280-2
TREH	ENST00000613915.4 linkuse as main transcript	n.*1234G>A		non_coding_transcript_exon_variant	11/13	2		ENSP00000477923.1	A0A087WTJ4
TREH	ENST00000613915.4 linkuse as main transcript	n.*1234G>A		3_prime_UTR_variant	11/13	2		ENSP00000477923.1	A0A087WTJ4

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000454

AC:

113

AN:

249170

Hom.:

AF XY:

0.000496

AC XY:

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00845

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000245

AC:

358

AN:

1461532

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

186

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00754

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000953

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000296

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000862

Hom.:

Bravo

AF:

0.000423

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000360

AC:

ExAC

AF:

0.000380

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign: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

Sep 14, 2021

The c.1457G>A (p.R486Q) alteration is located in exon 13 (coding exon 13) of the TREH gene. This alteration results from a G to A substitution at nucleotide position 1457, causing the arginine (R) at amino acid position 486 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

TREH-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 05, 2019

This variant is classified as likely 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

0.082

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.1

DANN

Benign

0.96

DEOGEN2

Benign

0.040

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0066

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.026

Sift

Benign

0.44

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.063

B;.

Vest4

0.085

MVP

0.11

MPC

0.034

ClinPred

0.0098

GERP RS

-2.6

Varity_R

0.041

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: -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