Variant 7-5308893-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080495.3(TNRC18):c.8682G>C(p.Gln2894His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000277 in 1,337,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

TNRC18
NM_001080495.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22474119).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC18	NM_001080495.3 link	c.8682G>C	p.Gln2894His	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.8682G>C	p.Gln2894His	missense_variant	Exon 29 of 30	5	NM_001080495.3	ENSP00000395538.1		O15417-1
TNRC18	ENST00000399537.8 link	c.8682G>C	p.Gln2894His	missense_variant	Exon 29 of 30	5		ENSP00000382452.4		H9KVB4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000277

AC:

AN:

1337492

Hom.:

Cov.:

AF XY:

0.0000256

AC XY:

AN XY:

663424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000347

Gnomad4 OTH exome

AF:

0.0000192

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8682G>C (p.Q2894H) alteration is located in exon 29 (coding exon 28) of the TNRC18 gene. This alteration results from a G to C substitution at nucleotide position 8682, causing the glutamine (Q) at amino acid position 2894 to be replaced by a histidine (H). 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

0.28

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

0.049

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;L

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.051

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.034

D;D

Polyphen

0.45

.;B

Vest4

0.51

MutPred

0.23

Loss of solvent accessibility (P = 0.0238);Loss of solvent accessibility (P = 0.0238);

MVP

0.043

MPC

0.50

ClinPred

0.67

GERP RS

3.9

Varity_R

0.26

gMVP

0.73

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