chr3-3129173-C-T

Variant names:

• chr3-3129173-C-T
• rs75033443
• NM_182916.3:c.133C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_182916.3(TRNT1):​c.133C>T​(p.Leu45Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,990 control chromosomes in the GnomAD database, including 410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (149 hom., cov: 34)
  • Exomes 𝑓: 0.012 (261 hom.)
• Consequence: TRNT1 NM_182916.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.508
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa and erythrocytic microcytosis

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 3-3129173-C-T is Benign according to our data. Variant chr3-3129173-C-T is described in ClinVar as Benign. ClinVar VariationId is 380598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.508 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182916.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNT1	NM_182916.3	MANE Select	c.133C>T	p.Leu45Leu	synonymous	Exon 2 of 8	NP_886552.3	Q96Q11-1
	TRNT1	NM_001367321.1		c.133C>T	p.Leu45Leu	synonymous	Exon 2 of 9	NP_001354250.1	Q96Q11-1
	TRNT1	NM_001367322.1		c.133C>T	p.Leu45Leu	synonymous	Exon 2 of 8	NP_001354251.1	Q96Q11-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNT1	ENST00000251607.11	TSL:1 MANE Select	c.133C>T	p.Leu45Leu	synonymous	Exon 2 of 8	ENSP00000251607.6	Q96Q11-1
	TRNT1	ENST00000280591.10	TSL:1	c.133C>T	p.Leu45Leu	synonymous	Exon 2 of 8	ENSP00000280591.6	Q96Q11-2
	TRNT1	ENST00000339437.11	TSL:1	c.133C>T	p.Leu45Leu	synonymous	Exon 2 of 3	ENSP00000342985.6	Q96Q11-3

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4677 AN: 152184 Hom.: 147 Cov.: 34

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0311

GnomAD2 exomes AF: 0.0125 AC: 3152 AN: 251428 AF XY: 0.0107

Gnomad AFR exome AF: 0.0915

Gnomad AMR exome AF: 0.0110

Gnomad ASJ exome AF: 0.00913

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00968

Gnomad OTH exome AF: 0.00977

GnomAD4 exome AF: 0.0123 AC: 17934 AN: 1461688 Hom.: 261 Cov.: 35 AF XY: 0.0118 AC XY: 8567 AN XY: 727144

African (AFR) AF: 0.0871 AC: 2914 AN: 33464

American (AMR) AF: 0.0121 AC: 540 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00930 AC: 243 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000441 AC: 38 AN: 86248

European-Finnish (FIN) AF: 0.00197 AC: 105 AN: 53418

Middle Eastern (MID) AF: 0.0113 AC: 65 AN: 5750

European-Non Finnish (NFE) AF: 0.0118 AC: 13133 AN: 1111886

Other (OTH) AF: 0.0148 AC: 896 AN: 60374

GnomAD4 genome AF: 0.0309 AC: 4702 AN: 152302 Hom.: 149 Cov.: 34 AF XY: 0.0289 AC XY: 2149 AN XY: 74470

African (AFR) AF: 0.0850 AC: 3534 AN: 41562

American (AMR) AF: 0.0229 AC: 350 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4832

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10598

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0104 AC: 706 AN: 68040

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0225 Hom.: 39

Bravo AF: 0.0350

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.0102

EpiControl AF: 0.0115

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	4.0
DANN	Benign	0.88
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75033443; hg19: chr3-3170857;