rs1669348

Positions:

chr3-3147714-A-G

Variant summary

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

The NM_182916.3(TRNT1):c.1056+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,597,412 control chromosomes in the GnomAD database, including 304,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23076 hom., cov: 32)

Exomes 𝑓: 0.61 ( 281629 hom. )

Consequence

TRNT1
NM_182916.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.271

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 3-3147714-A-G is Benign according to our data. Variant chr3-3147714-A-G is described in ClinVar as [Benign]. Clinvar id is 380146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNT1	NM_182916.3 linkuse as main transcript	c.1056+11A>G		intron_variant		ENST00000251607.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRNT1	ENST00000251607.11 linkuse as main transcript	c.1056+11A>G		intron_variant		1	NM_182916.3	P1	Q96Q11-1

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80819

AN:

151898

Hom.:

23082

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.705

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.584

GnomAD3 exomes

AF:

0.543

AC:

130231

AN:

240004

Hom.:

38024

AF XY:

0.556

AC XY:

72556

AN XY:

130522

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.702

Gnomad EAS exome

AF:

0.218

Gnomad SAS exome

AF:

0.479

Gnomad FIN exome

AF:

0.574

Gnomad NFE exome

AF:

0.664

Gnomad OTH exome

AF:

0.606

GnomAD4 exome

AF:

0.614

AC:

888059

AN:

1445396

Hom.:

281629

Cov.:

AF XY:

0.613

AC XY:

440417

AN XY:

718032

show subpopulations

Gnomad4 AFR exome

AF:

0.357

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.693

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.478

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.657

Gnomad4 OTH exome

AF:

0.602

GnomAD4 genome

AF:

0.532

AC:

80829

AN:

152016

Hom.:

23076

Cov.:

AF XY:

0.522

AC XY:

38823

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.367

Gnomad4 AMR

AF:

0.471

Gnomad4 ASJ

AF:

0.705

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.442

Gnomad4 FIN

AF:

0.568

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.584

Alfa

AF:

0.591

Hom.:

8753

Bravo

AF:

0.515

Asia WGS

AF:

0.342

AC:

1192

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 59% of patients studied by a panel of primary immunodeficiencies. Number of patients: 56. 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 -
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. -

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -

Retinitis pigmentosa and erythrocytic microcytosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.7

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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