11-118658926-C-A

Position:

chr11-118658926-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007180.3(TREH):c.1524G>T(p.Gln508His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,866 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

TREH
NM_007180.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -1.54

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033119082).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREH	NM_007180.3 linkuse as main transcript	c.1524G>T	p.Gln508His	missense_variant	13/15	ENST00000264029.9	NP_009111.2	O43280-1
TREH	NM_001301065.2 linkuse as main transcript	c.1431G>T	p.Gln477His	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.1524G>T	p.Gln508His	missense_variant	13/15	1	NM_007180.3	ENSP00000264029.5	O43280-1
TREH	ENST00000397925.2 linkuse as main transcript	c.1431G>T	p.Gln477His	missense_variant	12/14	1		ENSP00000381020.2	O43280-2
TREH	ENST00000613915.4 linkuse as main transcript	n.*1301G>T		non_coding_transcript_exon_variant	11/13	2		ENSP00000477923.1	A0A087WTJ4
TREH	ENST00000613915.4 linkuse as main transcript	n.*1301G>T		3_prime_UTR_variant	11/13	2		ENSP00000477923.1	A0A087WTJ4

Frequencies

GnomAD3 genomes

AF:

0.000742

AC:

113

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00145

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000449

AC:

112

AN:

249252

Hom.:

AF XY:

0.000458

AC XY:

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000947

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.00125

AC:

1826

AN:

1461642

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

906

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000375

Gnomad4 NFE exome

AF:

0.00160

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152224

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00145

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.000657

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000954

AC:

ExAC

AF:

0.000413

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.000652

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.1524G>T (p.Q508H) alteration is located in exon 13 (coding exon 13) of the TREH gene. This alteration results from a G to T substitution at nucleotide position 1524, causing the glutamine (Q) at amino acid position 508 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

TREH-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 29, 2024

The TREH c.1524G>T variant is predicted to result in the amino acid substitution p.Gln508His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.097% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.3

DANN

Benign

0.91

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.052

Sift

Benign

0.050

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.034

B;.

Vest4

0.21

MutPred

0.51

Loss of ubiquitination at K509 (P = 0.0683);.;

MVP

0.34

MPC

0.14

ClinPred

0.041

GERP RS

-6.4

Varity_R

0.068

gMVP

0.39

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