3-101565273-G-C

Position:

• chr3-101565273-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017819.4(TRMT10C):​c.492G>C​(p.Lys164Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,611,854 control chromosomes in the GnomAD database, including 96 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 Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (46 hom.)
• Consequence: TRMT10C NM_017819.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.587

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=0.0026145875).
• BP6: Variant 3-101565273-G-C is Benign according to our data. Variant chr3-101565273-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 377049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (2240/152228) while in subpopulation AFR AF= 0.0507 (2104/41524). AF 95% confidence interval is 0.0489. There are 50 homozygotes in gnomad4. There are 1030 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT10C	NM_017819.4	c.492G>C	p.Lys164Asn	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.492G>C	p.Lys164Asn	missense_variant	2/2	1	NM_017819.4	ENSP00000312356.6
TRMT10C	ENST00000495642.1	c.492G>C	p.Lys164Asn	missense_variant	2/2	3		ENSP00000419389.1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2236 AN: 152110 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00714

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00348 AC: 863 AN: 248000 Hom.: 17 AF XY: 0.00241 AC XY: 325 AN XY: 134718

Gnomad AFR exome AF: 0.0504

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000888

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00136 AC: 1983 AN: 1459626 Hom.: 46 Cov.: 33 AF XY: 0.00114 AC XY: 824 AN XY: 725976

Gnomad4 AFR exome AF: 0.0486

Gnomad4 AMR exome AF: 0.00297

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000333

Gnomad4 OTH exome AF: 0.00272

GnomAD4 genome AF: 0.0147 AC: 2240 AN: 152228 Hom.: 50 Cov.: 32 AF XY: 0.0138 AC XY: 1030 AN XY: 74426

Gnomad4 AFR AF: 0.0507

Gnomad4 AMR AF: 0.00713

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00213 Hom.: 9

Bravo AF: 0.0164

ESP6500AA AF: 0.0430 AC: 156

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00420 AC: 507

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 30, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 04, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.84
DANN	Benign	0.85
DEOGEN2	Benign	0.0052	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.25	T;T
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.014
Sift	Benign	0.37	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.0010	B;.
Vest4		0.037
MutPred		0.17		Loss of ubiquitination at K164 (P = 0.0027);Loss of ubiquitination at K164 (P = 0.0027);
MVP		0.048
MPC		0.19
ClinPred		0.0031	T
GERP RS		0.11
Varity_R		0.040
gMVP		0.18

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: rs16844031; hg19: chr3-101284117; COSMIC: COSV99047309;