NM_007180.3:c.1535T>A

Variant names:

• chr11-118658915-A-T
• rs556006762
• NM_007180.3:c.1535T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_007180.3(TREH):​c.1535T>A​(p.Met512Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TREH NM_007180.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.957

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREH	NM_007180.3	c.1535T>A	p.Met512Lys	missense_variant	Exon 13 of 15	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.1442T>A	p.Met481Lys	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.1535T>A	p.Met512Lys	missense_variant	Exon 13 of 15	1	NM_007180.3	ENSP00000264029.5
TREH	ENST00000397925.2	c.1442T>A	p.Met481Lys	missense_variant	Exon 12 of 14	1		ENSP00000381020.2
TREH	ENST00000613915.4	n.*1312T>A		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000477923.1
TREH	ENST00000613915.4	n.*1312T>A		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000477923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 249230 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135212

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

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: 0.00000885

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461610 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.63	T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Benign	-0.78	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.94
MutPred		0.86		Loss of stability (P = 0.0142);.;
MVP		0.40
MPC		0.28
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.97
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs556006762; hg19: chr11-118529624;