8-124451487-C-T

Variant names:

• chr8-124451487-C-T
• NM_017956.4:c.560C>T

Variant summary

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

The NM_017956.4(TRMT12):​c.560C>T​(p.Pro187Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRMT12 NM_017956.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12

Genes affected

TRMT12 (HGNC:26091): (tRNA methyltransferase 12 homolog) Wybutosine (yW) is a hypermodified guanosine at the 3-prime position adjacent to the anticodon of phenylalanine tRNA that stabilizes codon-anticodon interactions during decoding on the ribosome. TRMT12 is the human homolog of a yeast gene essential for yW synthesis (Noma and Suzuki, 2006).[supplied by OMIM, Mar 2008]

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
TRMT12	NM_017956.4	c.560C>T	p.Pro187Leu	missense_variant	Exon 1 of 1	ENST00000328599.4	NP_060426.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT12	ENST00000328599.4	c.560C>T	p.Pro187Leu	missense_variant	Exon 1 of 1	6	NM_017956.4	ENSP00000329858.3
TRMT12	ENST00000521443.1	n.438+230C>T		intron_variant	Intron 1 of 1	4
TRMT12	ENST00000522518.1	n.330+230C>T		intron_variant	Intron 1 of 2	3		ENSP00000429771.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461886 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.560C>T (p.P187L) alteration is located in exon 1 (coding exon 1) of the TRMT12 gene. This alteration results from a C to T substitution at nucleotide position 560, causing the proline (P) at amino acid position 187 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	4.0	H
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.35		Loss of disorder (P = 0.0302);
MVP		0.30
MPC		0.86
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.57
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-125463728;