chr3-101564948-C-G

Position:

• chr3-101564948-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017819.4(TRMT10C):​c.167C>G​(p.Pro56Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,613,228 control chromosomes in the GnomAD database, including 19,951 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1601 hom., cov: 31)
  • Exomes 𝑓: 0.16 (18350 hom.)
• Consequence: TRMT10C NM_017819.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.964

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010961294).
• BP6: Variant 3-101564948-C-G is Benign according to our data. Variant chr3-101564948-C-G is described in ClinVar as [Benign]. Clinvar id is 671432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT10C	NM_017819.4	c.167C>G	p.Pro56Arg	missense_variant	2/2	ENST00000309922.7	NP_060289.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT10C	ENST00000309922.7	c.167C>G	p.Pro56Arg	missense_variant	2/2	1	NM_017819.4	ENSP00000312356.6
TRMT10C	ENST00000495642.1	c.167C>G	p.Pro56Arg	missense_variant	2/2	3		ENSP00000419389.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21592 AN: 151528 Hom.: 1600 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.153

GnomAD3 exomes AF: 0.148 AC: 36857 AN: 249424 Hom.: 2934 AF XY: 0.153 AC XY: 20684 AN XY: 135334

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.0936

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.133

Gnomad SAS exome AF: 0.197

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.157 AC: 228824 AN: 1461580 Hom.: 18350 Cov.: 33 AF XY: 0.158 AC XY: 114755 AN XY: 727096

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0983

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.142 AC: 21601 AN: 151648 Hom.: 1601 Cov.: 31 AF XY: 0.143 AC XY: 10611 AN XY: 74090

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.152

Alfa AF: 0.143 Hom.: 1307

Bravo AF: 0.138

TwinsUK AF: 0.160 AC: 595

ALSPAC AF: 0.162 AC: 625

ESP6500AA AF: 0.102 AC: 381

ESP6500EA AF: 0.162 AC: 1330

ExAC AF: 0.150 AC: 18108

Asia WGS AF: 0.176 AC: 614 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.166

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.0015	T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.37	T;T
MetaRNN	Benign	0.0011	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.58	N;N
REVEL	Benign	0.098
Sift	Benign	0.22	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.0010	B;.
Vest4		0.016
MPC		0.17
ClinPred		0.0070	T
GERP RS		5.2
Varity_R		0.040
gMVP		0.082

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: rs3762735; hg19: chr3-101283792; COSMIC: COSV59305950;