Variant rs527655595 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_007180.3(TREH):c.90-9_106delTCTCTGCAGTGAGATTTACTGCCACG(p.Ser30fs) variant causes a frameshift, splice acceptor, splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 1,586,486 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00043 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 17 hom. )

Consequence

TREH
NM_007180.3 frameshift, splice_acceptor, splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided P:1U:1

Conservation

PhyloP100: 7.68

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:

TREH (HGNC:):

TREH links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREH	NM_007180.3 linkuse as main transcript	c.90-9_106delTCTCTGCAGTGAGATTTACTGCCACG	p.Ser30fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	2/15	ENST00000264029.9	NP_009111.2	O43280-1
TREH	NM_001301065.2 linkuse as main transcript	c.90-9_106delTCTCTGCAGTGAGATTTACTGCCACG	p.Ser30fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	2/14		NP_001287994.1	O43280-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9 linkuse as main transcript	c.90-9_106delTCTCTGCAGTGAGATTTACTGCCACG	p.Ser30fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	2/15	1	NM_007180.3	ENSP00000264029.5		O43280-1

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00135

AC:

278

AN:

205282

Hom.:

AF XY:

0.00165

AC XY:

181

AN XY:

109792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000337

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000133

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000111

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.000756

AC:

1085

AN:

1434262

Hom.:

AF XY:

0.00107

AC XY:

758

AN XY:

710424

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000245

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000104

Gnomad4 SAS exome

AF:

0.0123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000455

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.000434

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000151

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

alpha, alpha-Trehalase deficiency

Pathogenic:1Uncertain:1

Uncertain significance, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NG_023321.1(NM_007180.2):c.90-9_106del in the TREH gene has an allele frequency of 0.011 in South Asian subpopulation in the gnomAD database. Saleheen et al. identified six participants homozygous for c.90-9_106del in a cohort with a high rate of consanguinity (PMID: 28406212). We interpret it as a variant of uncertain significance in favor of likely pathogenic. ACMG/AMP criteria applied: BS1; PM3. -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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