rs334773

Positions:

chr3-3129108-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182916.3(TRNT1):c.68C>T(p.Pro23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,614,056 control chromosomes in the GnomAD database, including 783,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. P23A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.92 ( 64988 hom., cov: 32)

Exomes 𝑓: 0.99 ( 718699 hom. )

Consequence

TRNT1
NM_182916.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.876

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 links:

TRNT1 (HGNC:):

TRNT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.5487294E-7).

BP6

Variant 3-3129108-C-T is Benign according to our data. Variant chr3-3129108-C-T is described in ClinVar as [Benign]. Clinvar id is 403570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNT1	NM_182916.3 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	2/8	ENST00000251607.11	NP_886552.3	Q96Q11-1A0A024R2H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRNT1	ENST00000251607.11 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	2/8	1	NM_182916.3	ENSP00000251607.6		Q96Q11-1

Frequencies

GnomAD3 genomes

AF:

0.915

AC:

139197

AN:

152090

Hom.:

64946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.709

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.963

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.968

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.941

GnomAD3 exomes

AF:

0.977

AC:

245656

AN:

251472

Hom.:

120711

AF XY:

0.983

AC XY:

133652

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.698

Gnomad AMR exome

AF:

0.982

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.988

GnomAD4 exome

AF:

0.990

AC:

1447952

AN:

1461848

Hom.:

718699

Cov.:

AF XY:

0.992

AC XY:

721280

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.694

Gnomad4 AMR exome

AF:

0.979

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.979

GnomAD4 genome

AF:

0.915

AC:

139300

AN:

152208

Hom.:

64988

Cov.:

AF XY:

0.919

AC XY:

68381

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.709

Gnomad4 AMR

AF:

0.963

Gnomad4 ASJ

AF:

0.999

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.998

Gnomad4 OTH

AF:

0.941

Alfa

AF:

0.984

Hom.:

150573

Bravo

AF:

0.901

TwinsUK

AF:

0.999

AC:

3703

ALSPAC

AF:

0.999

AC:

3849

ESP6500AA

AF:

0.713

AC:

3142

ESP6500EA

AF:

0.998

AC:

8587

ExAC

AF:

0.972

AC:

118037

Asia WGS

AF:

0.983

AC:

3418

AN:

3478

EpiCase

AF:

0.998

EpiControl

AF:

0.997

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -

Retinitis pigmentosa and erythrocytic microcytosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.033

T;.;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.14

.;.;T;.;T;T

MetaRNN

Benign

5.5e-7

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

N;N;N;N;N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

0.33

N;N;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.73

T;T;T;T;T;T

Sift4G

Benign

0.86

T;T;T;T;T;T

Polyphen

0.0

B;.;B;.;.;.

Vest4

0.082

MPC

0.0049

ClinPred

0.0026

GERP RS

3.4

Varity_R

0.025

gMVP

0.28

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over