chr1-100133310-G-A

Position:

• chr1-100133310-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019083.3(TRMT13):​c.142G>A​(p.Ala48Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 1,612,804 control chromosomes in the GnomAD database, including 574,372 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A48V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.75 (45051 hom., cov: 30)
  • Exomes 𝑓: 0.85 (529321 hom.)
• Consequence: TRMT13 NM_019083.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.02

Genes affected

TRMT13 (HGNC:25502): (tRNA methyltransferase 13 homolog) Predicted to enable tRNA methyltransferase activity. Predicted to be involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.7824184E-7).
• BP6: Variant 1-100133310-G-A is Benign according to our data. Variant chr1-100133310-G-A is described in ClinVar as [Benign]. Clinvar id is 1233160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT13	NM_019083.3	c.142G>A	p.Ala48Thr	missense_variant	1/11	ENST00000370141.8	NP_061956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT13	ENST00000370141.8	c.142G>A	p.Ala48Thr	missense_variant	1/11	1	NM_019083.3	ENSP00000359160	P1
TRMT13	ENST00000370139.1	c.49G>A	p.Ala17Thr	missense_variant	1/6	3		ENSP00000359158
TRMT13	ENST00000370143.5	c.142G>A	p.Ala48Thr	missense_variant	1/5	3		ENSP00000359162
TRMT13	ENST00000482437.5	c.142G>A	p.Ala48Thr	missense_variant, NMD_transcript_variant	1/8	2		ENSP00000432616

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113325 AN: 151484 Hom.: 45038 Cov.: 30

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.852

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.783

GnomAD3 exomes AF: 0.851 AC: 212751 AN: 250012 Hom.: 92102 AF XY: 0.857 AC XY: 115792 AN XY: 135122

Gnomad AFR exome AF: 0.441

Gnomad AMR exome AF: 0.921

Gnomad ASJ exome AF: 0.890

Gnomad EAS exome AF: 0.958

Gnomad SAS exome AF: 0.894

Gnomad FIN exome AF: 0.884

Gnomad NFE exome AF: 0.849

Gnomad OTH exome AF: 0.856

GnomAD4 exome AF: 0.848 AC: 1239556 AN: 1461200 Hom.: 529321 Cov.: 54 AF XY: 0.851 AC XY: 618462 AN XY: 726864

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.915

Gnomad4 ASJ exome AF: 0.889

Gnomad4 EAS exome AF: 0.945

Gnomad4 SAS exome AF: 0.894

Gnomad4 FIN exome AF: 0.881

Gnomad4 NFE exome AF: 0.849

Gnomad4 OTH exome AF: 0.840

GnomAD4 genome AF: 0.748 AC: 113365 AN: 151604 Hom.: 45051 Cov.: 30 AF XY: 0.754 AC XY: 55857 AN XY: 74054

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.786

Alfa AF: 0.834 Hom.: 83654

Bravo AF: 0.734

TwinsUK AF: 0.849 AC: 3148

ALSPAC AF: 0.854 AC: 3292

ESP6500AA AF: 0.457 AC: 2012

ESP6500EA AF: 0.845 AC: 7271

ExAC AF: 0.838 AC: 101741

Asia WGS AF: 0.868 AC: 3018 AN: 3478

EpiCase AF: 0.850

EpiControl AF: 0.848

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.70	T;T;T
MetaRNN	Benign	5.8e-7	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.83	.;L;.
MutationTaster	Benign	0.93	P;P;P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.85	N;N;N
REVEL	Benign	0.015
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.20	.;B;.
Vest4		0.10
MPC		0.17
ClinPred		0.030	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs472498; hg19: chr1-100598866;