rs16844031

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 46 hom. )

Consequence

TRMT10C
NM_017819.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.587

Publications

6 publications found

Variant links:

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]

TRMT10C Gene-Disease associations (from GenCC):

combined oxidative phosphorylation defect type 30
Inheritance: Unknown, AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
mitochondrial disease
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

TRMT10C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT10C	NM_017819.4 link	c.492G>C	p.Lys164Asn	missense_variant	Exon 2 of 2	ENST00000309922.7	NP_060289.2	Q7L0Y3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT10C	ENST00000309922.7 link	c.492G>C	p.Lys164Asn	missense_variant	Exon 2 of 2	1	NM_017819.4	ENSP00000312356.6		Q7L0Y3
TRMT10C	ENST00000495642.1 link	c.492G>C	p.Lys164Asn	missense_variant	Exon 2 of 2	3		ENSP00000419389.1		C9JVB6

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2236

AN:

152110

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00348

AC:

863

AN:

248000

AF XY:

0.00241

show subpopulations

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 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.:

Cov.:

AF XY:

0.00114

AC XY:

824

AN XY:

725976

show subpopulations

African (AFR)

AF:

0.0486

AC:

1622

AN:

33396

American (AMR)

AF:

0.00297

AC:

132

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.000128

AC:

AN:

85618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00278

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

1111130

Other (OTH)

AF:

0.00272

AC:

164

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

100

201

301

402

502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0147

AC:

2240

AN:

152228

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1030

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0507

AC:

2104

AN:

41524

American (AMR)

AF:

0.00713

AC:

109

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68016

Other (OTH)

AF:

0.00900

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

110

220

330

440

550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.0164

ESP6500AA

AF:

0.0430

AC:

156

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00420

AC:

507

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 04, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 30, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.84

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0052

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.59

PrimateAI

Benign

0.21

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

GERP RS

0.11

Varity_R

0.040

gMVP

0.18

Mutation Taster

=99/1

polymorphism

(source)

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

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rs16844031

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over