chr11-118658994-G-C

Variant names:

• chr11-118658994-G-C
• rs2276064
• NM_007180.3:c.1456C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007180.3(TREH):​c.1456C>G​(p.Arg486Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 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. R486Q) 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: 0.0330
• Publications: 21 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0888018).

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.1456C>G	p.Arg486Gly	missense	Exon 13 of 15	NP_009111.2
	TREH	NM_001301065.2		c.1363C>G	p.Arg455Gly	missense	Exon 12 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.1456C>G	p.Arg486Gly	missense	Exon 13 of 15	ENSP00000264029.5
	TREH	ENST00000397925.2	TSL:1	c.1363C>G	p.Arg455Gly	missense	Exon 12 of 14	ENSP00000381020.2
	TREH	ENST00000613915.4	TSL:2	n.*1233C>G		non_coding_transcript_exon	Exon 11 of 13	ENSP00000477923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.9
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.033
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.036
Sift	Benign	0.27	T
Sift4G	Benign	0.24	T
Polyphen		0.0070	B
Vest4		0.11
MutPred		0.52		Loss of MoRF binding (P = 0.0258)
MVP		0.081
MPC		0.036
ClinPred		0.10	T
GERP RS		2.4
Varity_R		0.10
gMVP		0.38
Mutation Taster		=93/7	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: rs2276064; hg19: chr11-118529703;