Genetic Variant TNRC18:c.8700+3A>G (chr7-5308872-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001080495.3(TNRC18):c.8700+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNRC18
NM_001080495.3 splice_region, intron

Scores

Splicing: ADA: 0.9657

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.572

Publications

0 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:

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ACMG classification

Classification was made for transcript

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

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.8700+3A>G		splice_region intron	N/A	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.8700+3A>G		splice_region intron	N/A	ENSP00000395538.1	O15417-1
	TNRC18	ENST00000399537.8	TSL:5	c.8700+3A>G		splice_region intron	N/A	ENSP00000382452.4	H9KVB4

Frequencies

GnomAD3 genomes

AF:

0.000291

AC:

AN:

51524

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000385

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000277

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:

0.000336

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000215

AC:

AN:

186310

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000113

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: AS_VQSR

AF:

0.00000704

AC:

AN:

426016

Hom.:

Cov.:

AF XY:

0.00000453

AC XY:

AN XY:

220794

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

11732

American (AMR)

AF:

0.00

AC:

AN:

26222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9892

East Asian (EAS)

AF:

0.00

AC:

AN:

9898

South Asian (SAS)

AF:

0.0000225

AC:

AN:

44512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1174

European-Non Finnish (NFE)

AF:

0.00000708

AC:

AN:

282318

Other (OTH)

AF:

0.00

AC:

AN:

15964

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000291

AC:

AN:

51548

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

24676

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000385

AC:

AN:

12994

American (AMR)

AF:

0.000277

AC:

AN:

3612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1400

East Asian (EAS)

AF:

0.00

AC:

AN:

2004

South Asian (SAS)

AF:

0.00

AC:

AN:

1562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

110

European-Non Finnish (NFE)

AF:

0.000336

AC:

AN:

26802

Other (OTH)

AF:

0.00

AC:

AN:

668

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.238

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.57

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Pathogenic

0.80

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over