Variant 9-37777623-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_144964.4(TRMT10B):c.867C>A(p.Tyr289Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,613,866 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0024 ( 11 hom. )

Consequence

TRMT10B
NM_144964.4 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

TRMT10B (HGNC:26454): (tRNA methyltransferase 10B) Enables tRNA (guanine-N1-)-methyltransferase activity. Predicted to be involved in mitochondrial tRNA processing. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TRMT10B links:

EXOSC3 (HGNC:17944): (exosome component 3) This gene encodes a non-catalytic component of the human exosome, a complex with 3'-5' exoribonuclease activity that plays a role in numerous RNA processing and degradation activities. Related pseudogenes of this gene are found on chromosome 19 and 21. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2012]

EXOSC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 9-37777623-C-A is Benign according to our data. Variant chr9-37777623-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 801362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT10B	NM_144964.4 linkuse as main transcript	c.867C>A	p.Tyr289Ter	stop_gained	9/9	ENST00000297994.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT10B	ENST00000297994.4 linkuse as main transcript	c.867C>A	p.Tyr289Ter	stop_gained	9/9	1	NM_144964.4	P1	Q6PF06-1

Frequencies

GnomAD3 genomes

AF:

0.00210

AC:

320

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00973

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00210

AC:

523

AN:

249550

Hom.:

AF XY:

0.00220

AC XY:

298

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00891

Gnomad NFE exome

AF:

0.00238

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00240

AC:

3502

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1738

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.00800

Gnomad4 NFE exome

AF:

0.00251

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00210

AC:

320

AN:

152192

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00973

Gnomad4 NFE

AF:

0.00263

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00135

ExAC

AF:

0.00197

AC:

238

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	EXOSC3: BS2; TRMT10B: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.48

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.38

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.82

MutationTaster

Benign

1.0

D;D;D;D

Vest4

0.18

GERP RS

3.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over