chr3-3129173-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_182916.3(TRNT1):​c.133C>T​(p.Leu45Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,990 control chromosomes in the GnomAD database, including 410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 149 hom., cov: 34)
Exomes 𝑓: 0.012 ( 261 hom. )

Consequence

TRNT1
NM_182916.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.508

Publications

4 publications found
Variant links:
Genes affected
TRNT1 (HGNC:17341): (tRNA nucleotidyl transferase 1) The protein encoded by this gene is a CCA-adding enzyme which belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family. This essential enzyme functions by catalyzing the addition of the conserved nucleotide triplet CCA to the 3' terminus of tRNA molecules. Mutations in this gene result in sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
TRNT1 Gene-Disease associations (from GenCC):
  • congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
  • retinitis pigmentosa and erythrocytic microcytosis
    Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 3-3129173-C-T is Benign according to our data. Variant chr3-3129173-C-T is described in ClinVar as [Benign]. Clinvar id is 380598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.508 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRNT1NM_182916.3 linkc.133C>T p.Leu45Leu synonymous_variant Exon 2 of 8 ENST00000251607.11 NP_886552.3 Q96Q11-1A0A024R2H7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRNT1ENST00000251607.11 linkc.133C>T p.Leu45Leu synonymous_variant Exon 2 of 8 1 NM_182916.3 ENSP00000251607.6 Q96Q11-1

Frequencies

GnomAD3 genomes
AF:
0.0307
AC:
4677
AN:
152184
Hom.:
147
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0847
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0229
Gnomad ASJ
AF:
0.00720
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.000661
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.0104
Gnomad OTH
AF:
0.0311
GnomAD2 exomes
AF:
0.0125
AC:
3152
AN:
251428
AF XY:
0.0107
show subpopulations
Gnomad AFR exome
AF:
0.0915
Gnomad AMR exome
AF:
0.0110
Gnomad ASJ exome
AF:
0.00913
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00120
Gnomad NFE exome
AF:
0.00968
Gnomad OTH exome
AF:
0.00977
GnomAD4 exome
AF:
0.0123
AC:
17934
AN:
1461688
Hom.:
261
Cov.:
35
AF XY:
0.0118
AC XY:
8567
AN XY:
727144
show subpopulations
African (AFR)
AF:
0.0871
AC:
2914
AN:
33464
American (AMR)
AF:
0.0121
AC:
540
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00930
AC:
243
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.000441
AC:
38
AN:
86248
European-Finnish (FIN)
AF:
0.00197
AC:
105
AN:
53418
Middle Eastern (MID)
AF:
0.0113
AC:
65
AN:
5750
European-Non Finnish (NFE)
AF:
0.0118
AC:
13133
AN:
1111886
Other (OTH)
AF:
0.0148
AC:
896
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.460
Heterozygous variant carriers
0
764
1528
2293
3057
3821
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
558
1116
1674
2232
2790
<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
AF:
0.0309
AC:
4702
AN:
152302
Hom.:
149
Cov.:
34
AF XY:
0.0289
AC XY:
2149
AN XY:
74470
show subpopulations
African (AFR)
AF:
0.0850
AC:
3534
AN:
41562
American (AMR)
AF:
0.0229
AC:
350
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.00720
AC:
25
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.00145
AC:
7
AN:
4832
European-Finnish (FIN)
AF:
0.000661
AC:
7
AN:
10598
Middle Eastern (MID)
AF:
0.0272
AC:
8
AN:
294
European-Non Finnish (NFE)
AF:
0.0104
AC:
706
AN:
68040
Other (OTH)
AF:
0.0307
AC:
65
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
213
426
638
851
1064
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
54
108
162
216
270
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0225
Hom.:
39
Bravo
AF:
0.0350
Asia WGS
AF:
0.00635
AC:
22
AN:
3478
EpiCase
AF:
0.0102
EpiControl
AF:
0.0115

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Dec 22, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mar 29, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:2
Oct 17, 2023
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
4.0
DANN
Benign
0.88
PhyloP100
0.51
Mutation Taster
=100/0
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

Publications

Other links and lift over

dbSNP: rs75033443; hg19: chr3-3170857; API