dbSNP rs1322080089: TRMT1L:p.Thr600Ala (chr1-185123881-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030934.5(TRMT1L):c.1798A>G(p.Thr600Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,362,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TRMT1L
NM_030934.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0450

Publications

0 publications found

Variant links:

Genes affected

TRMT1L (HGNC:16782): (tRNA methyltransferase 1 like) This gene encodes a protein that has some similarity to N2,N2-dimethylguanosine tRNA methyltransferase from other organisms. Studies of the mouse ortholog have shown that this protein plays a role in motor coordination and exploratory behavior, and it may also be involved in modulating postnatal neuronal functions. Alternatively spliced transcripts have been identified for this gene. [provided by RefSeq, Jan 2011]

TRMT1L links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08944011).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030934.5. 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
	TRMT1L	NM_030934.5	MANE Select	c.1798A>G	p.Thr600Ala	missense	Exon 13 of 15	NP_112196.3
	TRMT1L	NM_001202423.2		c.1330A>G	p.Thr444Ala	missense	Exon 13 of 15	NP_001189352.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRMT1L	ENST00000367506.10	TSL:1 MANE Select	c.1798A>G	p.Thr600Ala	missense	Exon 13 of 15	ENSP00000356476.5	Q7Z2T5-1
TRMT1L	ENST00000942796.1		c.1861A>G	p.Thr621Ala	missense	Exon 14 of 16	ENSP00000612855.1
TRMT1L	ENST00000860207.1		c.1795A>G	p.Thr599Ala	missense	Exon 13 of 15	ENSP00000530266.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

143146

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000293

AC:

AN:

1362860

Hom.:

Cov.:

AF XY:

0.00000297

AC XY:

AN XY:

674084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29932

American (AMR)

AF:

0.00

AC:

AN:

26756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24442

East Asian (EAS)

AF:

0.00

AC:

AN:

35694

South Asian (SAS)

AF:

0.0000546

AC:

AN:

73214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1062972

Other (OTH)

AF:

0.00

AC:

AN:

56534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.47

M_CAP

Benign

0.0037

MetaRNN

Benign

0.089

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.22

PhyloP100

-0.045

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.57

REVEL

Benign

0.053

Sift

Benign

0.077

Sift4G

Benign

0.53

Polyphen

0.0020

Vest4

0.063

MutPred

0.36

Loss of glycosylation at T600 (P = 0.0923)

MVP

0.043

MPC

0.31

ClinPred

0.086

GERP RS

1.0

Varity_R

0.028

gMVP

0.20

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over