Variant chr11-118658395-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007180.3(TREH):c.1646G>A(p.Arg549His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,610,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TREH
NM_007180.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.435

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07783911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREH	NM_007180.3 linkuse as main transcript	c.1646G>A	p.Arg549His	missense_variant	15/15	ENST00000264029.9	NP_009111.2	O43280-1
TREH	NM_001301065.2 linkuse as main transcript	c.1553G>A	p.Arg518His	missense_variant	14/14		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.1646G>A	p.Arg549His	missense_variant	15/15	1	NM_007180.3	ENSP00000264029.5	O43280-1
TREH	ENST00000397925.2 linkuse as main transcript	c.1553G>A	p.Arg518His	missense_variant	14/14	1		ENSP00000381020.2	O43280-2
TREH	ENST00000613915.4 linkuse as main transcript	n.*1423G>A		non_coding_transcript_exon_variant	13/13	2		ENSP00000477923.1	A0A087WTJ4
TREH	ENST00000613915.4 linkuse as main transcript	n.*1423G>A		3_prime_UTR_variant	13/13	2		ENSP00000477923.1	A0A087WTJ4

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000901

AC:

AN:

244122

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

132636

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.0000878

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000267

Gnomad FIN exome

AF:

0.0000484

Gnomad NFE exome

AF:

0.0000723

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000108

AC:

157

AN:

1458060

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

725122

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000675

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000383

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000908

AC:

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

Aug 20, 2024

The c.1646G>A (p.R549H) alteration is located in exon 15 (coding exon 15) of the TREH gene. This alteration results from a G to A substitution at nucleotide position 1646, causing the arginine (R) at amino acid position 549 to be replaced by a histidine (H). 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

Benign

0.078

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.043

Sift

Benign

0.063

T;T

Sift4G

Uncertain

0.036

D;T

Polyphen

0.12

B;.

Vest4

0.047

MVP

0.50

MPC

0.036

ClinPred

0.15

GERP RS

3.4

Varity_R

0.098

gMVP

0.35

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