chr11-118659447-G-T

Variant names:

• chr11-118659447-G-T
• rs782653438
• NM_007180.3:c.1355C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_007180.3(TREH):​c.1355C>A​(p.Pro452Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,112 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: 6.9e-7 (0 hom.)
• Consequence: TREH NM_007180.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.56

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREH	NM_007180.3	c.1355C>A	p.Pro452Gln	missense_variant	Exon 12 of 15	ENST00000264029.9	NP_009111.2
TREH	NM_001301065.2	c.1262C>A	p.Pro421Gln	missense_variant	Exon 11 of 14		NP_001287994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREH	ENST00000264029.9	c.1355C>A	p.Pro452Gln	missense_variant	Exon 12 of 15	1	NM_007180.3	ENSP00000264029.5
TREH	ENST00000397925.2	c.1262C>A	p.Pro421Gln	missense_variant	Exon 11 of 14	1		ENSP00000381020.2
TREH	ENST00000613915.4	n.*1132C>A		non_coding_transcript_exon_variant	Exon 10 of 13	2		ENSP00000477923.1
TREH	ENST00000613915.4	n.*1132C>A		3_prime_UTR_variant	Exon 10 of 13	2		ENSP00000477923.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454112 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722496

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.42	T
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-7.7	D;D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.73
MutPred		0.72		Gain of relative solvent accessibility (P = 0.09);.;
MVP		0.52
MPC		0.24
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.57
gMVP		0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs782653438; hg19: chr11-118530156;