rs11827611

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007180.3(TREH):c.1345T>C(p.Tyr449His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,604,718 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 33)

Exomes 𝑓: 0.00098 ( 14 hom. )

Consequence

TREH
NM_007180.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.138

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042777956).

BP6

Variant 11-118659457-A-G is Benign according to our data. Variant chr11-118659457-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 376781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00999 (1521/152248) while in subpopulation AFR AF= 0.0345 (1431/41536). AF 95% confidence interval is 0.033. There are 19 homozygotes in gnomad4. There are 693 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREH	NM_007180.3 link	c.1345T>C	p.Tyr449His	missense_variant	Exon 12 of 15	ENST00000264029.9	NP_009111.2	O43280-1
TREH	NM_001301065.2 link	c.1252T>C	p.Tyr418His	missense_variant	Exon 11 of 14		NP_001287994.1	O43280-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TREH	ENST00000264029.9 link	c.1345T>C	p.Tyr449His	missense_variant	Exon 12 of 15	1	NM_007180.3	ENSP00000264029.5	O43280-1
TREH	ENST00000397925.2 link	c.1252T>C	p.Tyr418His	missense_variant	Exon 11 of 14	1		ENSP00000381020.2	O43280-2
TREH	ENST00000613915.4 link	n.*1122T>C		non_coding_transcript_exon_variant	Exon 10 of 13	2		ENSP00000477923.1	A0A087WTJ4
TREH	ENST00000613915.4 link	n.*1122T>C		3_prime_UTR_variant	Exon 10 of 13	2		ENSP00000477923.1	A0A087WTJ4

Frequencies

GnomAD3 genomes

AF:

0.00998

AC:

1519

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00253

AC:

596

AN:

236032

Hom.:

AF XY:

0.00182

AC XY:

233

AN XY:

127928

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000655

Gnomad OTH exome

AF:

0.000347

GnomAD4 exome

AF:

0.000980

AC:

1423

AN:

1452470

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

610

AN XY:

721428

show subpopulations

Gnomad4 AFR exome

AF:

0.0347

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000524

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00999

AC:

1521

AN:

152248

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

693

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0345

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00218

Hom.:

Bravo

AF:

0.0111

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0338

AC:

130

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00289

AC:

349

Asia WGS

AF:

0.00173

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

Oct 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.1

DANN

Benign

0.85

DEOGEN2

Benign

0.076

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.32

PROVEAN

Benign

0.34

N;N

REVEL

Benign

0.057

Sift

Benign

0.083

T;T

Sift4G

Benign

0.075

T;T

Polyphen

0.0010

B;.

Vest4

0.11

MVP

0.11

MPC

0.037

ClinPred

0.0033

GERP RS

-9.0

Varity_R

0.047

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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