3-101565205-G-A

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.424G>A(p.Val142Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRMT10C NM_017819.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.98

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=0.039313823).
• BP6: Variant 3-101565205-G-A is Benign according to our data. Variant chr3-101565205-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2529656.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.424G>A	p.Val142Met	missense_variant	2/2	ENST00000309922.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT10C	ENST00000309922.7	c.424G>A	p.Val142Met	missense_variant	2/2	1	NM_017819.4	P1
TRMT10C	ENST00000495642.1	c.424G>A	p.Val142Met	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.99e-7 AC: 1 AN: 1429680 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 710812

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: 0.00

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 32

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

Mar 24, 2023

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	0.086
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.0010
Dann	Benign	0.30
DEOGEN2	Benign	0.00076	T;.
Eigen	Benign	-3.1
Eigen_PC	Benign	-3.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.20	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.69	N;N
REVEL	Benign	0.060
Sift	Benign	0.32	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.0	B;.
Vest4		0.039
MutPred		0.38		Loss of methylation at K143 (P = 0.0169);Loss of methylation at K143 (P = 0.0169);
MVP		0.14
MPC		0.16
ClinPred		0.47	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.099

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-101284049;