chr3-3129173-C-T

Variant names:

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

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)

TRNT1 links:

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
TRNT1	NM_182916.3 link	c.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
TRNT1	ENST00000251607.11 link	c.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.:

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.:

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:

AN:

39696

South Asian (SAS)

AF:

0.000441

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00197

AC:

105

AN:

53418

Middle Eastern (MID)

AF:

0.0113

AC:

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

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

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.:

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:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000661

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0104

AC:

706

AN:

68040

Other (OTH)

AF:

0.0307

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

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

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.:

Bravo

AF:

0.0350

Asia WGS

AF:

0.00635

AC:

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

(source)

DANN

Benign

0.88

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over