11-118658994-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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREH	NM_007180.3	c.1456C>G	p.Arg486Gly	missense_variant	Exon 13 of 15	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.1363C>G	p.Arg455Gly	missense_variant	Exon 12 of 14		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.1456C>G	p.Arg486Gly	missense_variant	Exon 13 of 15	1	NM_007180.3	ENSP00000264029.5
TREH	ENST00000397925.2	c.1363C>G	p.Arg455Gly	missense_variant	Exon 12 of 14	1		ENSP00000381020.2
TREH	ENST00000613915.4	n.*1233C>G		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000477923.1
TREH	ENST00000613915.4	n.*1233C>G		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000477923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.
PhyloP100		0.033
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.036
Sift	Benign	0.27	T;T
Sift4G	Benign	0.24	T;T
Vest4		0.11
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;