rs780447209

Variant names:

• chr9-37763715-T-A
• rs780447209
• NM_144964.4:c.382T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-37763715-T-A
• chr9-37763715-T-C

Variant summary

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

The NM_144964.4(TRMT10B):​c.382T>A​(p.Cys128Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. C128R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT10B NM_144964.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29
• Publications: 0 publications found

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]

ENSG00000255872 (HGNC:):

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: Illumina, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT10B	NM_144964.4	MANE Select	c.382T>A	p.Cys128Ser	missense	Exon 4 of 9	NP_659401.2	Q6PF06-1
	TRMT10B	NM_001286950.2		c.382T>A	p.Cys128Ser	missense	Exon 4 of 8	NP_001273879.1	Q6PF06-5
	TRMT10B	NM_001286951.2		c.97T>A	p.Cys33Ser	missense	Exon 3 of 8	NP_001273880.1	Q6PF06-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT10B	ENST00000297994.4	TSL:1 MANE Select	c.382T>A	p.Cys128Ser	missense	Exon 4 of 9	ENSP00000297994.3	Q6PF06-1
	TRMT10B	ENST00000488673.6	TSL:1	n.382T>A		non_coding_transcript_exon	Exon 4 of 9	ENSP00000437395.1	Q6PF06-3
	ENSG00000255872	ENST00000540557.1	TSL:5	n.*910+20199A>T		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.028	D
Polyphen		0.83	P
Vest4		0.59
MutPred		0.64		Gain of disorder (P = 0.0033)
MVP		0.54
MPC		0.24
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.87
gMVP		0.68
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs780447209; hg19: chr9-37763712;