3-3128776-A-AGTT

Variant names:

• chr3-3128776-A-AGTT
• rs3884411
• NM_182916.3:c.-27-237_-27-235dupGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_182916.3(TRNT1):​c.-27-237_-27-235dupGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.91 (64832 hom., cov: 0)
• Consequence: TRNT1 NM_182916.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54
• Publications: 0 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: Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• retinitis pigmentosa and erythrocytic microcytosis

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-3128776-A-AGTT is Benign according to our data. Variant chr3-3128776-A-AGTT is described in ClinVar as [Benign]. Clinvar id is 1269795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNT1	NM_182916.3	c.-27-237_-27-235dupGTT		intron_variant	Intron 1 of 7	ENST00000251607.11	NP_886552.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRNT1	ENST00000251607.11	c.-27-238_-27-237insGTT		intron_variant	Intron 1 of 7	1	NM_182916.3	ENSP00000251607.6

Frequencies

GnomAD3 genomes AF: 0.915 AC: 138884 AN: 151788 Hom.: 64790 Cov.: 0

Gnomad AFR AF: 0.708

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.915 AC: 138987 AN: 151906 Hom.: 64832 Cov.: 0 AF XY: 0.919 AC XY: 68211 AN XY: 74256

African (AFR) AF: 0.708 AC: 29246 AN: 41294

American (AMR) AF: 0.962 AC: 14688 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3467 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5153 AN: 5154

South Asian (SAS) AF: 0.999 AC: 4811 AN: 4816

European-Finnish (FIN) AF: 1.00 AC: 10567 AN: 10568

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67864 AN: 68018

Other (OTH) AF: 0.941 AC: 1992 AN: 2116

Alfa AF: 0.942 Hom.: 7348

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3884411; hg19: chr3-3170460;