3-3126942-C-A

Position:

• chr3-3126942-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182916.3(TRNT1):​c.-76C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 152,836 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (156 hom., cov: 33)
  • Exomes 𝑓: 0.014 (2 hom.)
• Consequence: TRNT1 NM_182916.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.64

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 3-3126942-C-A is Benign according to our data. Variant chr3-3126942-C-A is described in ClinVar as [Benign]. Clinvar id is 1326594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNT1	NM_182916.3	c.-76C>A		5_prime_UTR_variant	1/8	ENST00000251607.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRNT1	ENST00000251607.11	c.-76C>A		5_prime_UTR_variant	1/8	1	NM_182916.3	P1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4752 AN: 152226 Hom.: 154 Cov.: 33

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0315

GnomAD4 exome AF: 0.0142 AC: 7 AN: 492 Hom.: 2 Cov.: 0 AF XY: 0.0137 AC XY: 5 AN XY: 366

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00966

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0313 AC: 4775 AN: 152344 Hom.: 156 Cov.: 33 AF XY: 0.0294 AC XY: 2191 AN XY: 74500

Gnomad4 AFR AF: 0.0866

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.00340 Hom.: 0

Bravo AF: 0.0356

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 24, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.5
DANN	Benign	0.88

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

Other links and lift over

dbSNP: rs116700990; hg19: chr3-3168626;