3-3128725-G-T

Variant names:

• chr3-3128725-G-T
• rs334774
• NM_182916.3:c.-27-289G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182916.3(TRNT1):​c.-27-289G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 31)
• Consequence: TRNT1 NM_182916.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 2 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine
• retinitis pigmentosa and erythrocytic microcytosis

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

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.-27-289G>T		intron	N/A	NP_886552.3	Q96Q11-1
	TRNT1	NM_001367321.1		c.-27-289G>T		intron	N/A	NP_001354250.1	Q96Q11-1
	TRNT1	NM_001367322.1		c.-27-289G>T		intron	N/A	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.-27-289G>T		intron	N/A	ENSP00000251607.6	Q96Q11-1
	TRNT1	ENST00000280591.10	TSL:1	c.-27-289G>T		intron	N/A	ENSP00000280591.6	Q96Q11-2
	TRNT1	ENST00000339437.11	TSL:1	c.-27-289G>T		intron	N/A	ENSP00000342985.6	Q96Q11-3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151848 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151848 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74124

African (AFR) AF: 0.00 AC: 0 AN: 41304

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 1435

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.97
DANN	Benign	0.23
PhyloP100		-0.54

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

Other links and lift over

dbSNP: rs334774; hg19: chr3-3170409;