Variant rs34978247 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007180.3(TREH):c.419A>G(p.Lys140Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00563 in 1,584,382 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0058 ( 24 hom. )

Consequence

TREH
NM_007180.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.44

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007879496).

BP6

Variant 11-118662885-T-C is Benign according to our data. Variant chr11-118662885-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 377170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-118662885-T-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 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.419A>G	p.Lys140Arg	missense_variant	4/15	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2 linkuse as main transcript	c.419A>G	p.Lys140Arg	missense_variant	4/14		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9 linkuse as main transcript	c.419A>G	p.Lys140Arg	missense_variant	4/15	1	NM_007180.3	ENSP00000264029	P1	O43280-1

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

552

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00607

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00349

AC:

708

AN:

202860

Hom.:

AF XY:

0.00344

AC XY:

376

AN XY:

109164

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.00238

Gnomad ASJ exome

AF:

0.00681

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000269

Gnomad FIN exome

AF:

0.00142

Gnomad NFE exome

AF:

0.00574

Gnomad OTH exome

AF:

0.00436

GnomAD4 exome

AF:

0.00584

AC:

8370

AN:

1432030

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

3979

AN XY:

709552

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00263

Gnomad4 ASJ exome

AF:

0.00679

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000280

Gnomad4 FIN exome

AF:

0.00143

Gnomad4 NFE exome

AF:

0.00698

Gnomad4 OTH exome

AF:

0.00462

GnomAD4 genome

AF:

0.00361

AC:

550

AN:

152352

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

234

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00607

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00563

Hom.:

Bravo

AF:

0.00380

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000753

AC:

ESP6500EA

AF:

0.00577

AC:

ExAC

AF:

0.00280

AC:

337

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 17, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0079

T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

0.88

N;N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.031

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0040

B;.

Vest4

0.17

MVP

0.030

MPC

0.029

ClinPred

0.0061

GERP RS

2.4

Varity_R

0.063

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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