chr3-3140611-G-T

Position:

• chr3-3140611-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000251607.11(TRNT1):​c.444G>T​(p.Ala148=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,613,944 control chromosomes in the GnomAD database, including 609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A148A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.040 (242 hom., cov: 34)
  • Exomes 𝑓: 0.016 (367 hom.)
• Consequence: TRNT1 ENST00000251607.11 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.578

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 3-3140611-G-T is Benign according to our data. Variant chr3-3140611-G-T is described in ClinVar as [Benign]. Clinvar id is 380599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.578 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNT1	NM_182916.3	c.444G>T	p.Ala148=	synonymous_variant	4/8	ENST00000251607.11	NP_886552.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRNT1	ENST00000251607.11	c.444G>T	p.Ala148=	synonymous_variant	4/8	1	NM_182916.3	ENSP00000251607	P1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5986 AN: 152134 Hom.: 239 Cov.: 34

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0291

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0162 AC: 4063 AN: 251422 Hom.: 102 AF XY: 0.0140 AC XY: 1905 AN XY: 135892

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.00933

Gnomad EAS exome AF: 0.00288

Gnomad SAS exome AF: 0.00317

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.0123

Gnomad OTH exome AF: 0.0132

GnomAD4 exome AF: 0.0155 AC: 22698 AN: 1461692 Hom.: 367 Cov.: 31 AF XY: 0.0150 AC XY: 10884 AN XY: 727156

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.00953

Gnomad4 EAS exome AF: 0.00154

Gnomad4 SAS exome AF: 0.00347

Gnomad4 FIN exome AF: 0.00210

Gnomad4 NFE exome AF: 0.0148

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome AF: 0.0395 AC: 6015 AN: 152252 Hom.: 242 Cov.: 34 AF XY: 0.0372 AC XY: 2769 AN XY: 74434

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0290

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.000849

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0215 Hom.: 41

Bravo AF: 0.0448

Asia WGS AF: 0.0220 AC: 75 AN: 3478

EpiCase AF: 0.0136

EpiControl AF: 0.0136

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 22, 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	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 -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Retinal dystrophy Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.0
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

Other links and lift over

dbSNP: rs41399044; hg19: chr3-3182295;