dbSNP rs3884411: TRNT1:c.-27-237_-27-235dupGTT (chr3-3128776-A-AGTT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.54

Publications

0 publications found

Variant links:

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)

TRNT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRNT1	NM_182916.3	MANE Select	c.-27-237_-27-235dupGTT	intron	N/A	NP_886552.3	Q96Q11-1
TRNT1	NM_001367321.1		c.-27-237_-27-235dupGTT	intron	N/A	NP_001354250.1	Q96Q11-1
TRNT1	NM_001367322.1		c.-27-237_-27-235dupGTT	intron	N/A	NP_001354251.1	Q96Q11-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRNT1	ENST00000251607.11	TSL:1 MANE Select	c.-27-238_-27-237insGTT	intron	N/A	ENSP00000251607.6	Q96Q11-1
TRNT1	ENST00000280591.10	TSL:1	c.-27-238_-27-237insGTT	intron	N/A	ENSP00000280591.6	Q96Q11-2
TRNT1	ENST00000339437.11	TSL:1	c.-27-238_-27-237insGTT	intron	N/A	ENSP00000342985.6	Q96Q11-3

Frequencies

GnomAD3 genomes

AF:

0.915

AC:

138884

AN:

151788

Hom.:

64790

Cov.:

show subpopulations

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.:

AF XY:

0.919

AC XY:

68211

AN XY:

74256

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

467

934

1402

1869

2336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.942

Hom.:

7348

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over