9-37761968-G-A

Position:

• chr9-37761968-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000297994.4(TRMT10B):​c.37G>A​(p.Glu13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT10B ENST00000297994.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.121029824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT10B	NM_144964.4	c.37G>A	p.Glu13Lys	missense_variant	2/9	ENST00000297994.4	NP_659401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT10B	ENST00000297994.4	c.37G>A	p.Glu13Lys	missense_variant	2/9	1	NM_144964.4	ENSP00000297994.3
ENSG00000255872	ENST00000540557.1	n.*910+21946C>T		intron_variant		5		ENSP00000457548.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.37G>A (p.E13K) alteration is located in exon 2 (coding exon 1) of the TRMT10B gene. This alteration results from a G to A substitution at nucleotide position 37, causing the glutamic acid (E) at amino acid position 13 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0049	.;.;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.62	N;N;N
REVEL	Benign	0.053
Sift	Pathogenic	0.0	D;D;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.099	.;.;B
Vest4		0.27
MutPred		0.23		Gain of MoRF binding (P = 0.0066);Gain of MoRF binding (P = 0.0066);Gain of MoRF binding (P = 0.0066);
MVP		0.014
MPC		0.050
ClinPred		0.70	D
GERP RS		4.6
Varity_R		0.11
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-37761965;