rs199730889

chr3-101565323-G-Achr3-101565323-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_017819.4(TRMT10C):c.542G>A(p.Arg181Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. R181L) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: TRMT10C NM_017819.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31

Genes affected

TRMT10C (HGNC:26022): (tRNA methyltransferase 10C, mitochondrial RNase P subunit) This gene encodes the precursor of a subunit of the mitochondrial ribonuclease P, which is involved in 5' processing of mitochondrial tRNAs. The encoded protein may confer RNA-binding capacity to mitochondrial ribonuclease P and may be essential for transcript processing, RNA modification, translation and mitochondrial respiration. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr3-101565323-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 224316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.17427182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT10C	NM_017819.4	c.542G>A	p.Arg181Gln	missense_variant	2/2	ENST00000309922.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT10C	ENST00000309922.7	c.542G>A	p.Arg181Gln	missense_variant	2/2	1	NM_017819.4	P1
TRMT10C	ENST00000495642.1	c.542G>A	p.Arg181Gln	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248734 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135012

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: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461194 Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7 AN XY: 726878

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: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.056	T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.094
Sift	Benign	0.12	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.40	B;.
Vest4		0.061
MutPred		0.55		Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);
MVP		0.33
MPC		0.20
ClinPred		0.46	T
GERP RS		4.8
Varity_R		0.12
gMVP		0.24

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: rs199730889; hg19: chr3-101284167; COSMIC: COSV59305130;