Variant rs2276064 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007180.3(TREH):c.1456C>T(p.Arg486Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 1,613,748 control chromosomes in the GnomAD database, including 7,497 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.039 ( 681 hom., cov: 33)

Exomes 𝑓: 0.037 ( 6816 hom. )

Consequence

TREH
NM_007180.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0330

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00507015).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREH	NM_007180.3 linkuse as main transcript	c.1456C>T	p.Arg486Trp	missense_variant	13/15	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2 linkuse as main transcript	c.1363C>T	p.Arg455Trp	missense_variant	12/14		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9 linkuse as main transcript	c.1456C>T	p.Arg486Trp	missense_variant	13/15	1	NM_007180.3	ENSP00000264029	P1	O43280-1
TREH	ENST00000397925.2 linkuse as main transcript	c.1363C>T	p.Arg455Trp	missense_variant	12/14	1		ENSP00000381020		O43280-2
TREH	ENST00000613915.4 linkuse as main transcript	c.*1233C>T		3_prime_UTR_variant, NMD_transcript_variant	11/13	2		ENSP00000477923

Frequencies

GnomAD3 genomes

AF:

0.0390

AC:

5932

AN:

152138

Hom.:

679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00637

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0767

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.0506

Gnomad FIN

AF:

0.00527

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.0421

GnomAD3 exomes

AF:

0.0860

AC:

21421

AN:

249154

Hom.:

3311

AF XY:

0.0743

AC XY:

10043

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.00478

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.0762

Gnomad EAS exome

AF:

0.409

Gnomad SAS exome

AF:

0.0429

Gnomad FIN exome

AF:

0.00594

Gnomad NFE exome

AF:

0.0151

Gnomad OTH exome

AF:

0.0572

GnomAD4 exome

AF:

0.0365

AC:

53413

AN:

1461492

Hom.:

6816

Cov.:

AF XY:

0.0356

AC XY:

25887

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.00376

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.0759

Gnomad4 EAS exome

AF:

0.470

Gnomad4 SAS exome

AF:

0.0414

Gnomad4 FIN exome

AF:

0.00708

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.0413

GnomAD4 genome

AF:

0.0390

AC:

5934

AN:

152256

Hom.:

681

Cov.:

AF XY:

0.0419

AC XY:

3117

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00635

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.0767

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.0502

Gnomad4 FIN

AF:

0.00527

Gnomad4 NFE

AF:

0.0139

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0362

Hom.:

1197

Bravo

AF:

0.0536

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00551

AC:

ESP6500EA

AF:

0.0183

AC:

152

ExAC

AF:

0.0763

AC:

9225

Asia WGS

AF:

0.191

AC:

664

AN:

3478

EpiCase

AF:

0.0162

EpiControl

AF:

0.0142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.049

T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.031

Sift

Benign

0.16

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.076

B;.

Vest4

0.068

MPC

0.032

ClinPred

0.0059

GERP RS

2.4

Varity_R

0.076

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over