rs10790256

Variant names:

• chr11-118663373-C-T
• rs10790256
• NM_007180.3:c.156G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_007180.3(TREH):​c.156G>A​(p.Lys52Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,595,466 control chromosomes in the GnomAD database, including 41,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (3024 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38312 hom.)
• Consequence: TREH NM_007180.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.65
• Publications: 36 publications found

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 Gene-Disease associations (from GenCC):

• diarrhea-vomiting due to trehalase deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 11-118663373-C-T is Benign according to our data. Variant chr11-118663373-C-T is described in ClinVar as Benign. ClinVar VariationId is 3035110.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007180.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREH	NM_007180.3	MANE Select	c.156G>A	p.Lys52Lys	synonymous	Exon 2 of 15	NP_009111.2
	TREH	NM_001301065.2		c.156G>A	p.Lys52Lys	synonymous	Exon 2 of 14	NP_001287994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREH	ENST00000264029.9	TSL:1 MANE Select	c.156G>A	p.Lys52Lys	synonymous	Exon 2 of 15	ENSP00000264029.5
	TREH	ENST00000397925.2	TSL:1	c.156G>A	p.Lys52Lys	synonymous	Exon 2 of 14	ENSP00000381020.2
	TREH	ENST00000531295.5	TSL:5	n.175G>A		non_coding_transcript_exon	Exon 2 of 10

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27787 AN: 152046 Hom.: 3022 Cov.: 32

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.185

GnomAD2 exomes AF: 0.221 AC: 49119 AN: 222254 AF XY: 0.230

Gnomad AFR exome AF: 0.0495

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.244

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.226 AC: 325950 AN: 1443302 Hom.: 38312 Cov.: 34 AF XY: 0.230 AC XY: 164437 AN XY: 715816

African (AFR) AF: 0.0469 AC: 1557 AN: 33218

American (AMR) AF: 0.203 AC: 8573 AN: 42238

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 5171 AN: 25662

East Asian (EAS) AF: 0.220 AC: 8597 AN: 39122

South Asian (SAS) AF: 0.337 AC: 27766 AN: 82472

European-Finnish (FIN) AF: 0.220 AC: 11490 AN: 52206

Middle Eastern (MID) AF: 0.217 AC: 1250 AN: 5754

European-Non Finnish (NFE) AF: 0.225 AC: 248129 AN: 1102840

Other (OTH) AF: 0.224 AC: 13417 AN: 59790

GnomAD4 genome AF: 0.183 AC: 27793 AN: 152164 Hom.: 3024 Cov.: 32 AF XY: 0.187 AC XY: 13919 AN XY: 74392

African (AFR) AF: 0.0561 AC: 2330 AN: 41538

American (AMR) AF: 0.224 AC: 3417 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 696 AN: 3472

East Asian (EAS) AF: 0.243 AC: 1261 AN: 5180

South Asian (SAS) AF: 0.358 AC: 1723 AN: 4814

European-Finnish (FIN) AF: 0.216 AC: 2285 AN: 10572

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15463 AN: 67988

Other (OTH) AF: 0.187 AC: 395 AN: 2110

Alfa AF: 0.205 Hom.: 4809

Bravo AF: 0.172

Asia WGS AF: 0.266 AC: 924 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TREH-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10790256; hg19: chr11-118534082; COSMIC: COSV50620151;