chr9-37762634-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144964.4(TRMT10B):c.244A>G(p.Lys82Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000025 in 1,597,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TRMT10B
NM_144964.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.11

Publications

1 publications found

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:

ENSG00000255872 (HGNC:):

ENSG00000255872 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 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia type 1B
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Illumina, Genomics England PanelApp, G2P
pontocerebellar hypoplasia type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EXOSC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2144523).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144964.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRMT10B	NM_144964.4	MANE Select	c.244A>G	p.Lys82Glu	missense	Exon 3 of 9	NP_659401.2	Q6PF06-1
TRMT10B	NM_001286950.2		c.244A>G	p.Lys82Glu	missense	Exon 3 of 8	NP_001273879.1	Q6PF06-5
TRMT10B	NM_001286954.2		c.68A>G	p.Gln23Arg	missense	Exon 3 of 8	NP_001273883.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRMT10B	ENST00000297994.4	TSL:1 MANE Select	c.244A>G	p.Lys82Glu	missense	Exon 3 of 9	ENSP00000297994.3	Q6PF06-1
TRMT10B	ENST00000488673.6	TSL:1	n.244A>G		non_coding_transcript_exon	Exon 3 of 9	ENSP00000437395.1	Q6PF06-3
ENSG00000255872	ENST00000540557.1	TSL:5	n.*910+21280T>C		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000444

AC:

AN:

225294

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000744

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445714

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716904

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

42560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25746

East Asian (EAS)

AF:

0.00

AC:

AN:

39512

South Asian (SAS)

AF:

0.00

AC:

AN:

83180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103286

Other (OTH)

AF:

0.00

AC:

AN:

59934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41458

American (AMR)

AF:

0.0000655

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000275

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000830

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.012

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.3

PhyloP100

5.1

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

REVEL

Benign

0.093

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.057

Polyphen

0.86

Vest4

0.47

MVP

0.25

MPC

0.25

ClinPred

0.78

GERP RS

3.7

Varity_R

0.52

gMVP

0.49

Mutation Taster

=72/28

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over