1-185140076-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_030934.5(TRMT1L):ā€‹c.1006A>Gā€‹(p.Lys336Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

TRMT1L
NM_030934.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03855157).
BP6
Variant 1-185140076-T-C is Benign according to our data. Variant chr1-185140076-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2320737.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRMT1LNM_030934.5 linkuse as main transcriptc.1006A>G p.Lys336Glu missense_variant 8/15 ENST00000367506.10 NP_112196.3 Q7Z2T5-1
TRMT1LNM_001202423.2 linkuse as main transcriptc.538A>G p.Lys180Glu missense_variant 8/15 NP_001189352.1 Q7Z2T5B4DXX1
TRMT1LXM_047431291.1 linkuse as main transcriptc.538A>G p.Lys180Glu missense_variant 8/15 XP_047287247.1
TRMT1LXM_047431292.1 linkuse as main transcriptc.538A>G p.Lys180Glu missense_variant 8/15 XP_047287248.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRMT1LENST00000367506.10 linkuse as main transcriptc.1006A>G p.Lys336Glu missense_variant 8/151 NM_030934.5 ENSP00000356476.5 Q7Z2T5-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 26, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.049
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
13
DANN
Benign
0.24
DEOGEN2
Benign
0.092
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.0057
N
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.92
N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.73
N
REVEL
Benign
0.066
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.11
MutPred
0.39
Loss of ubiquitination at K336 (P = 0.0155);
MVP
0.043
MPC
0.44
ClinPred
0.022
T
GERP RS
2.8
Varity_R
0.039
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1652997787; hg19: chr1-185109208; API