Genetic Variant TNRC18:p.Glu2952Lys (chr7-5308159-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080495.3(TNRC18):c.8854G>A(p.Glu2952Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNRC18
NM_001080495.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41584682).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080495.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC18	NM_001080495.3	MANE Select	c.8854G>A	p.Glu2952Lys	missense	Exon 30 of 30	NP_001073964.2	O15417-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC18	ENST00000430969.6	TSL:5 MANE Select	c.8854G>A	p.Glu2952Lys	missense	Exon 30 of 30	ENSP00000395538.1	O15417-1
	TNRC18	ENST00000399537.8	TSL:5	c.8854G>A	p.Glu2952Lys	missense	Exon 30 of 30	ENSP00000382452.4	H9KVB4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

194368

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1423754

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704966

African (AFR)

AF:

0.00

AC:

AN:

32576

American (AMR)

AF:

0.00

AC:

AN:

38874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25494

East Asian (EAS)

AF:

0.00

AC:

AN:

37636

South Asian (SAS)

AF:

0.00

AC:

AN:

81276

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4184

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094006

Other (OTH)

AF:

0.00

AC:

AN:

58880

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.42

MetaSVM

Uncertain

0.21

MutationAssessor

Benign

0.35

PhyloP100

7.3

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.63

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.46

MutPred

0.42

Gain of methylation at E2952 (P = 0.0153)

MVP

0.27

MPC

0.61

ClinPred

0.91

GERP RS

3.6

Varity_R

0.29

gMVP

0.85

Mutation Taster

=74/26

polymorphism

(source)

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

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