NM_144964.4:c.382T>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT10B	NM_144964.4	c.382T>A	p.Cys128Ser	missense_variant	Exon 4 of 9	ENST00000297994.4	NP_659401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT10B	ENST00000297994.4	c.382T>A	p.Cys128Ser	missense_variant	Exon 4 of 9	1	NM_144964.4	ENSP00000297994.3
ENSG00000255872	ENST00000540557.1	n.*910+20199A>T		intron_variant	Intron 9 of 11	5		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 v4.3

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;D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.2	D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.028	D;T;T
Polyphen		0.83, 0.97	.;P;D
Vest4		0.59
MutPred		0.64		Gain of disorder (P = 0.0033);.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs780447209; hg19: chr9-37763712;