chr11-118658925-TC-AA

Position:

• chr11-118658925-TC-AA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007180.3(TREH):​c.1524_1525delGAinsTT​(p.GlnLys508*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TREH NM_007180.3 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREH	NM_007180.3	c.1524_1525delGAinsTT	p.GlnLys508*	stop_gained		ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.1431_1432delGAinsTT	p.GlnLys477*	stop_gained			NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.1524_1525delGAinsTT	p.GlnLys508*	stop_gained		1	NM_007180.3	ENSP00000264029.5
TREH	ENST00000397925.2	c.1431_1432delGAinsTT	p.GlnLys477*	stop_gained		1		ENSP00000381020.2
TREH	ENST00000613915.4	n.*1301_*1302delGAinsTT		non_coding_transcript_exon_variant	11/13	2		ENSP00000477923.1
TREH	ENST00000613915.4	n.*1301_*1302delGAinsTT		3_prime_UTR_variant	11/13	2		ENSP00000477923.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

TREH-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 15, 2024

The TREH c.1524_1525delinsTT variant is predicted to result in an in-frame deletion and insertion. To our knowledge, this variant has not been reported in the literature. In gnomAD, this variant is likely reported as two separate variants c.1524G>T (p.Gln508His) and c.1525A>T (p.Lys509*); these variants are both reported in 0.097% of alleles in individuals of European (Non-Finnish) descent and are noted to be on the same haplotype in at least 112 instances (11-118529634-T-A; 11-118529635-C-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118529634;