NM_007180.3:c.1696C>T

Variant names:

• chr11-118658345-G-A
• rs200772007
• NM_007180.3:c.1696C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_007180.3(TREH):​c.1696C>T​(p.His566Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,600,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (0 hom.)
• Consequence: TREH NM_007180.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 1.29
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050507784).
• BS2: High AC in GnomAd4 at 43 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREH	NM_007180.3	MANE Select	c.1696C>T	p.His566Tyr	missense	Exon 15 of 15	NP_009111.2	O43280-1
	TREH	NM_001301065.2		c.1603C>T	p.His535Tyr	missense	Exon 14 of 14	NP_001287994.1	O43280-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREH	ENST00000264029.9	TSL:1 MANE Select	c.1696C>T	p.His566Tyr	missense	Exon 15 of 15	ENSP00000264029.5	O43280-1
	TREH	ENST00000397925.2	TSL:1	c.1603C>T	p.His535Tyr	missense	Exon 14 of 14	ENSP00000381020.2	O43280-2
	TREH	ENST00000854539.1		c.1543C>T	p.His515Tyr	missense	Exon 14 of 14	ENSP00000524598.1

Frequencies

GnomAD3 genomes AF: 0.000282 AC: 43 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000175 AC: 39 AN: 223172 AF XY: 0.000132

Gnomad AFR exome AF: 0.000232

Gnomad AMR exome AF: 0.000250

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000279

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000394 AC: 571 AN: 1447716 Hom.: 0 Cov.: 31 AF XY: 0.000366 AC XY: 263 AN XY: 718824

African (AFR) AF: 0.000121 AC: 4 AN: 33170

American (AMR) AF: 0.000258 AC: 11 AN: 42712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.00 AC: 0 AN: 39050

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4856

European-Non Finnish (NFE) AF: 0.000492 AC: 544 AN: 1106158

Other (OTH) AF: 0.000184 AC: 11 AN: 59824

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152336 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74498

African (AFR) AF: 0.000241 AC: 10 AN: 41568

American (AMR) AF: 0.000131 AC: 2 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000531 Hom.: 0

Bravo AF: 0.000249

ESP6500AA AF: 0.000705 AC: 3

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.000116 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)
-	-	1	TREH-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.073
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.49	T
Polyphen		0.70	P
Vest4		0.15
MVP		0.30
MPC		0.089
ClinPred		0.057	T
GERP RS		1.4
Varity_R		0.037
gMVP		0.55
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs200772007; hg19: chr11-118529054;