11-118658703-C-T

Variant names:

• chr11-118658703-C-T
• rs782641610
• NM_007180.3:c.1576G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007180.3(TREH):​c.1576G>A​(p.Gly526Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,802 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TREH NM_007180.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREH	NM_007180.3	c.1576G>A	p.Gly526Arg	missense_variant	Exon 14 of 15	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.1483G>A	p.Gly495Arg	missense_variant	Exon 13 of 14		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.1576G>A	p.Gly526Arg	missense_variant	Exon 14 of 15	1	NM_007180.3	ENSP00000264029.5
TREH	ENST00000397925.2	c.1483G>A	p.Gly495Arg	missense_variant	Exon 13 of 14	1		ENSP00000381020.2
TREH	ENST00000613915.4	n.*1353G>A		non_coding_transcript_exon_variant	Exon 12 of 13	2		ENSP00000477923.1
TREH	ENST00000613915.4	n.*1353G>A		3_prime_UTR_variant	Exon 12 of 13	2		ENSP00000477923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000875 AC: 2 AN: 228566 Hom.: 0 AF XY: 0.0000161 AC XY: 2 AN XY: 124172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000195

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1448802 Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2 AN XY: 719804

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.68	T
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.079	T;D
Polyphen		0.70	P;.
Vest4		0.55
MutPred		0.70		Gain of solvent accessibility (P = 0.0171);.;
MVP		0.48
MPC		0.25
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.69
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs782641610; hg19: chr11-118529412; COSMIC: COSV50620702; COSMIC: COSV50620702;