chr3-3147595-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182916.3(TRNT1):c.948A>G(p.Ala316Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,613,574 control chromosomes in the GnomAD database, including 541,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 43385 hom., cov: 31)

Exomes 𝑓: 0.82 ( 498155 hom. )

Consequence

TRNT1
NM_182916.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 0.905

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:

CRBN (HGNC:30185): (cereblon) This gene encodes a protein related to the Lon protease protein family. In rodents and other mammals this gene product is found in the cytoplasm localized with a calcium channel membrane protein, and is thought to play a role in brain development. Mutations in this gene are associated with autosomal recessive nonsyndromic cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

CRBN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 3-3147595-A-G is Benign according to our data. Variant chr3-3147595-A-G is described in ClinVar as [Benign]. Clinvar id is 380145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.905 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNT1	NM_182916.3 link	c.948A>G	p.Ala316Ala	synonymous_variant	Exon 7 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.948A>G	p.Ala316Ala	synonymous_variant	Exon 7 of 8	1	NM_182916.3	ENSP00000251607.6		Q96Q11-1

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

112629

AN:

151880

Hom.:

43370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.760

Gnomad ASJ

AF:

0.866

Gnomad EAS

AF:

0.939

Gnomad SAS

AF:

0.821

Gnomad FIN

AF:

0.799

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.837

Gnomad OTH

AF:

0.758

GnomAD3 exomes

AF:

0.799

AC:

200214

AN:

250614

Hom.:

81203

AF XY:

0.810

AC XY:

109941

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.686

Gnomad ASJ exome

AF:

0.862

Gnomad EAS exome

AF:

0.941

Gnomad SAS exome

AF:

0.816

Gnomad FIN exome

AF:

0.798

Gnomad NFE exome

AF:

0.841

Gnomad OTH exome

AF:

0.820

GnomAD4 exome

AF:

0.823

AC:

1202908

AN:

1461576

Hom.:

498155

Cov.:

AF XY:

0.825

AC XY:

599669

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.695

Gnomad4 ASJ exome

AF:

0.862

Gnomad4 EAS exome

AF:

0.936

Gnomad4 SAS exome

AF:

0.819

Gnomad4 FIN exome

AF:

0.800

Gnomad4 NFE exome

AF:

0.835

Gnomad4 OTH exome

AF:

0.817

GnomAD4 genome

AF:

0.741

AC:

112687

AN:

151998

Hom.:

43385

Cov.:

AF XY:

0.744

AC XY:

55282

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.760

Gnomad4 ASJ

AF:

0.866

Gnomad4 EAS

AF:

0.938

Gnomad4 SAS

AF:

0.820

Gnomad4 FIN

AF:

0.799

Gnomad4 NFE

AF:

0.837

Gnomad4 OTH

AF:

0.761

Alfa

AF:

0.822

Hom.:

118180

Bravo

AF:

0.724

Asia WGS

AF:

0.835

AC:

2905

AN:

3476

EpiCase

AF:

0.837

EpiControl

AF:

0.841

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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. -
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 96% of patients studied by a panel of primary immunodeficiencies. Number of patients: 91. Only high quality variants are reported. -

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -

not provided

Benign:1Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinitis pigmentosa and erythrocytic microcytosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.1

DANN

Benign

0.83

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