3-3128947-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_182916.3(TRNT1):c.-27-67C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,165,454 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (75 hom.)
• Consequence: TRNT1 NM_182916.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.821

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-3128947-C-G is Benign according to our data. Variant chr3-3128947-C-G is described in ClinVar as [Benign]. Clinvar id is 1297783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00637 (970/152248) while in subpopulation NFE AF= 0.0045 (306/68014). AF 95% confidence interval is 0.00408. There are 20 homozygotes in gnomad4. There are 625 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNT1	NM_182916.3	c.-27-67C>G		intron_variant		ENST00000251607.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRNT1	ENST00000251607.11	c.-27-67C>G		intron_variant		1	NM_182916.3	P1

Frequencies

GnomAD3 genomes AF: 0.00638 AC: 970 AN: 152130 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00450

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00509 AC: 5159 AN: 1013206 Hom.: 75 AF XY: 0.00494 AC XY: 2501 AN XY: 506644

Gnomad4 AFR exome AF: 0.000291

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.0000587

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000781

Gnomad4 FIN exome AF: 0.0560

Gnomad4 NFE exome AF: 0.00315

Gnomad4 OTH exome AF: 0.00466

GnomAD4 genome AF: 0.00637 AC: 970 AN: 152248 Hom.: 20 Cov.: 33 AF XY: 0.00840 AC XY: 625 AN XY: 74430

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0557

Gnomad4 NFE AF: 0.00450

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00737 Hom.: 1

Bravo AF: 0.00201

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.71
Dann	Benign	0.57

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: rs186544049; hg19: chr3-3170631;