chr1-100133311-C-T

Variant names:

• chr1-100133311-C-T
• rs687513
• NM_019083.3:c.143C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019083.3(TRMT13):​c.143C>T​(p.Ala48Val) 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 1,612,780 control chromosomes in the GnomAD database, including 574,372 homozygotes. 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A48T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.75 (45050 hom., cov: 30)
  • Exomes 𝑓: 0.85 (529322 hom.)
• Consequence: TRMT13 NM_019083.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.2916547E-7).
• BP6: Variant 1-100133311-C-T is Benign according to our data. Variant chr1-100133311-C-T is described in ClinVar as Benign. ClinVar VariationId is 1295596.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019083.3. 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
	TRMT13	NM_019083.3	MANE Select	c.143C>T	p.Ala48Val	missense	Exon 1 of 11	NP_061956.2	Q9NUP7-1
	TRMT13	NM_001393409.1		c.143C>T	p.Ala48Val	missense	Exon 1 of 11	NP_001380338.1
	TRMT13	NM_001393410.1		c.143C>T	p.Ala48Val	missense	Exon 1 of 9	NP_001380339.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT13	ENST00000370141.8	TSL:1 MANE Select	c.143C>T	p.Ala48Val	missense	Exon 1 of 11	ENSP00000359160.2	Q9NUP7-1
	TRMT13	ENST00000962881.1		c.143C>T	p.Ala48Val	missense	Exon 1 of 11	ENSP00000632940.1
	TRMT13	ENST00000370139.1	TSL:3	c.50C>T	p.Ala17Val	missense	Exon 1 of 6	ENSP00000359158.1	Q5VVK9

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113327 AN: 151478 Hom.: 45037 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: 0.785

GnomAD2 exomes AF: 0.851 AC: 212744 AN: 250002 AF XY: 0.857

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 FIN exome AF: 0.884

Gnomad NFE exome AF: 0.849

Gnomad OTH exome AF: 0.856

GnomAD4 exome AF: 0.848 AC: 1239550 AN: 1461182 Hom.: 529322 Cov.: 54 AF XY: 0.851 AC XY: 618464 AN XY: 726862

African (AFR) AF: 0.435 AC: 14568 AN: 33474

American (AMR) AF: 0.915 AC: 40822 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 23231 AN: 26130

East Asian (EAS) AF: 0.945 AC: 37463 AN: 39662

South Asian (SAS) AF: 0.894 AC: 77064 AN: 86218

European-Finnish (FIN) AF: 0.881 AC: 47038 AN: 53366

Middle Eastern (MID) AF: 0.812 AC: 4677 AN: 5762

European-Non Finnish (NFE) AF: 0.849 AC: 943972 AN: 1111572

Other (OTH) AF: 0.840 AC: 50715 AN: 60368

GnomAD4 genome AF: 0.748 AC: 113367 AN: 151598 Hom.: 45050 Cov.: 30 AF XY: 0.754 AC XY: 55862 AN XY: 74060

African (AFR) AF: 0.448 AC: 18512 AN: 41310

American (AMR) AF: 0.852 AC: 12992 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3089 AN: 3470

East Asian (EAS) AF: 0.946 AC: 4843 AN: 5122

South Asian (SAS) AF: 0.896 AC: 4309 AN: 4810

European-Finnish (FIN) AF: 0.886 AC: 9308 AN: 10508

Middle Eastern (MID) AF: 0.862 AC: 250 AN: 290

European-Non Finnish (NFE) AF: 0.850 AC: 57686 AN: 67844

Other (OTH) AF: 0.788 AC: 1653 AN: 2098

Alfa AF: 0.823 Hom.: 157722

Bravo AF: 0.734

TwinsUK AF: 0.849 AC: 3149

ALSPAC AF: 0.854 AC: 3292

ESP6500AA AF: 0.456 AC: 2009

ESP6500EA AF: 0.845 AC: 7268

ExAC AF: 0.838 AC: 101743

Asia WGS AF: 0.868 AC: 3018 AN: 3478

EpiCase AF: 0.850

EpiControl AF: 0.848

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.046
Eigen_PC	Benign	0.083
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	6.3e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.035
Sift	Benign	0.093	T
Sift4G	Benign	0.19	T
Polyphen		0.33	B
Vest4		0.24
MPC		0.19
ClinPred		0.052	T
GERP RS		5.0
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.38
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs687513; hg19: chr1-100598867; COSMIC: COSV104381391; COSMIC: COSV104381391;