dbSNP rs776254990: TRNT1:p.His9Gln (chr3-3129067-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182916.3(TRNT1):c.27C>G(p.His9Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. H9H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

TRNT1
NM_182916.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.571

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: 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 (MetaRNN=0.062043548).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
TRNT1	NM_182916.3	MANE Select	c.27C>G	p.His9Gln	missense	Exon 2 of 8	NP_886552.3	Q96Q11-1
TRNT1	NM_001367321.1		c.27C>G	p.His9Gln	missense	Exon 2 of 9	NP_001354250.1	Q96Q11-1
TRNT1	NM_001367322.1		c.27C>G	p.His9Gln	missense	Exon 2 of 8	NP_001354251.1	Q96Q11-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRNT1	ENST00000251607.11	TSL:1 MANE Select	c.27C>G	p.His9Gln	missense	Exon 2 of 8	ENSP00000251607.6	Q96Q11-1
TRNT1	ENST00000280591.10	TSL:1	c.27C>G	p.His9Gln	missense	Exon 2 of 8	ENSP00000280591.6	Q96Q11-2
TRNT1	ENST00000339437.11	TSL:1	c.27C>G	p.His9Gln	missense	Exon 2 of 3	ENSP00000342985.6	Q96Q11-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000207

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.041

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.46

M_CAP

Benign

0.0043

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

PhyloP100

0.57

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.96

REVEL

Benign

0.054

Sift

Benign

0.41

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.077

MutPred

0.40

Gain of sheet (P = 0.1208)

MVP

0.095

MPC

0.0049

ClinPred

0.19

GERP RS

-1.1

Varity_R

0.050

gMVP

0.53

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over