NM_001134665.3:c.955C>T

Variant names:

• chr4-99549153-G-A
• NM_001134665.3:c.955C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134665.3(TRMT10A):​c.955C>T​(p.Pro319Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT10A NM_001134665.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

Genes affected

TRMT10A (HGNC:28403): (tRNA methyltransferase 10A) This gene encodes a protein that belongs to the tRNA (Guanine-1)-methyltransferase family. A similar gene in yeast modifies several different tRNA species. Mutations in this gene are associated with microcephaly, short stature, and impaired glucose metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044152856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT10A	NM_001134665.3	c.955C>T	p.Pro319Ser	missense_variant	Exon 8 of 8	ENST00000394876.7	NP_001128137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT10A	ENST00000394876.7	c.955C>T	p.Pro319Ser	missense_variant	Exon 8 of 8	1	NM_001134665.3	ENSP00000378342.2
TRMT10A	ENST00000273962.7	c.955C>T	p.Pro319Ser	missense_variant	Exon 8 of 8	1		ENSP00000273962.3
TRMT10A	ENST00000394877.7	c.955C>T	p.Pro319Ser	missense_variant	Exon 8 of 8	2		ENSP00000378343.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.4
DANN	Benign	0.60
DEOGEN2	Benign	0.0048	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.55	.;.;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.010	N;N;N
REVEL	Benign	0.012
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.78	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.047
MutPred		0.11		Gain of glycosylation at S318 (P = 0.0026);Gain of glycosylation at S318 (P = 0.0026);Gain of glycosylation at S318 (P = 0.0026);
MVP		0.030
MPC		0.14
ClinPred		0.17	T
GERP RS		-1.3
Varity_R		0.033
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr4-100470310;