Variant 7-5308906-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080495.3(TNRC18):c.8669G>A(p.Arg2890Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,605,386 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

TNRC18
NM_001080495.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Variant links:

Genes affected

TNRC18 (HGNC:11962): (trinucleotide repeat containing 18) Predicted to enable chromatin binding activity. Located in cytosol; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TNRC18 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04566428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC18	NM_001080495.3 link	c.8669G>A	p.Arg2890Gln	missense_variant	Exon 29 of 30	ENST00000430969.6	NP_001073964.2	O15417-1A3KMH2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC18	ENST00000430969.6 link	c.8669G>A	p.Arg2890Gln	missense_variant	Exon 29 of 30	5	NM_001080495.3	ENSP00000395538.1		O15417-1
TNRC18	ENST00000399537.8 link	c.8669G>A	p.Arg2890Gln	missense_variant	Exon 29 of 30	5		ENSP00000382452.4		H9KVB4

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151830

Hom.:

Cov.:

show subpopulations

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000210

AC:

305

AN:

1453556

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

153

AN XY:

722440

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000354

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000234

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151830

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000382

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8669G>A (p.R2890Q) alteration is located in exon 29 (coding exon 28) of the TNRC18 gene. This alteration results from a G to A substitution at nucleotide position 8669, causing the arginine (R) at amino acid position 2890 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.81

.;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.071

Sift

Benign

0.63

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.010

.;B

Vest4

0.25

MutPred

0.22

Loss of MoRF binding (P = 0.014);Loss of MoRF binding (P = 0.014);

MVP

0.043

MPC

0.62

ClinPred

0.094

GERP RS

2.8

Varity_R

0.043

gMVP

0.22

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over