chr9-37776285-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144964.4(TRMT10B):c.724G>A(p.Val242Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,384,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V242L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TRMT10B
NM_144964.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.57

Publications

0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.724G>A	p.Val242Met	missense	Exon 8 of 9	NP_659401.2	Q6PF06-1
TRMT10B	NM_001286950.2		c.571G>A	p.Val191Met	missense	Exon 7 of 8	NP_001273879.1	Q6PF06-5
TRMT10B	NM_001286952.2		c.490G>A	p.Val164Met	missense	Exon 6 of 7	NP_001273881.1	Q6PF06-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRMT10B	ENST00000297994.4	TSL:1 MANE Select	c.724G>A	p.Val242Met	missense	Exon 8 of 9	ENSP00000297994.3	Q6PF06-1
TRMT10B	ENST00000488673.6	TSL:1	n.*311G>A		non_coding_transcript_exon	Exon 8 of 9	ENSP00000437395.1	Q6PF06-3
TRMT10B	ENST00000488673.6	TSL:1	n.*311G>A		3_prime_UTR	Exon 8 of 9	ENSP00000437395.1	Q6PF06-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000582

AC:

AN:

171926

AF XY:

0.0000107

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1384048

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

685460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29710

American (AMR)

AF:

0.00

AC:

AN:

30066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23570

East Asian (EAS)

AF:

0.00

AC:

AN:

36032

South Asian (SAS)

AF:

0.0000274

AC:

AN:

73118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5502

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078454

Other (OTH)

AF:

0.00

AC:

AN:

56988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000829

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0083

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

2.6

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.27

REVEL

Benign

0.036

Sift

Benign

0.096

Sift4G

Benign

0.13

Polyphen

0.061

Vest4

0.35

MutPred

0.52

Loss of methylation at K241 (P = 0.0165)

MVP

0.28

MPC

0.096

ClinPred

0.45

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.31

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over