11-118658395-C-G

Variant names:

• chr11-118658395-C-G
• rs566037210
• NM_007180.3:c.1646G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007180.3(TREH):​c.1646G>C​(p.Arg549Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R549H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TREH NM_007180.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.1646G>C	p.Arg549Pro	missense	Exon 15 of 15	NP_009111.2	O43280-1
	TREH	NM_001301065.2		c.1553G>C	p.Arg518Pro	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.1646G>C	p.Arg549Pro	missense	Exon 15 of 15	ENSP00000264029.5	O43280-1
	TREH	ENST00000397925.2	TSL:1	c.1553G>C	p.Arg518Pro	missense	Exon 14 of 14	ENSP00000381020.2	O43280-2
	TREH	ENST00000854539.1		c.1493G>C	p.Arg498Pro	missense	Exon 14 of 14	ENSP00000524598.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.00060	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.025
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.83	T
PhyloP100		-0.43
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.24
Sift	Benign	0.033	D
Sift4G	Benign	0.062	T
Polyphen		0.99	D
Vest4		0.49
MutPred		0.64		Loss of stability (P = 0.0351)
MVP		0.65
MPC		0.22
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.88
gMVP		0.81
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs566037210; hg19: chr11-118529104;