3-101564884-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_017819.4(TRMT10C):c.103A>G(p.Ile35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: TRMT10C NM_017819.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043178916).
• BP6: Variant 3-101564884-A-G is Benign according to our data. Variant chr3-101564884-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2221990.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT10C	NM_017819.4	c.103A>G	p.Ile35Val	missense_variant	2/2	ENST00000309922.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT10C	ENST00000309922.7	c.103A>G	p.Ile35Val	missense_variant	2/2	1	NM_017819.4	P1
TRMT10C	ENST00000495642.1	c.103A>G	p.Ile35Val	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 249466 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135340

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: 0.0000265

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461826 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727212

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: 0.0000497

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000248 AC: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.0020
Dann	Benign	0.23
DEOGEN2	Benign	0.000088	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.17	N;N
REVEL	Benign	0.0090
Sift	Benign	0.82	T;T
Sift4G	Benign	0.87	T;T
Polyphen		0.0	B;.
Vest4		0.021
MVP		0.072
MPC		0.13
ClinPred		0.022	T
GERP RS		-8.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.012
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs779037332; hg19: chr3-101283728;