dbSNP rs560820937: TNRC18:c.8700+3A>C (chr7-5308872-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP3BP6

The NM_001080495.3(TNRC18):c.8700+3A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000504 in 478,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

TNRC18
NM_001080495.3 splice_region, intron

Scores

Splicing: ADA: 0.9896

Clinical Significance

Likely benign no assertion criteria provided B:2

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 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.

BP6

Variant 7-5308872-T-G is Benign according to our data. Variant chr7-5308872-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1206354.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Frequencies

GnomAD3 genomes

AF:

0.000522

AC:

AN:

51762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000537

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00256

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00833

Gnomad NFE

AF:

0.000371

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000279

AC:

AN:

186310

AF XY:

0.000303

show subpopulations

Gnomad AFR exome

AF:

0.0000953

Gnomad AMR exome

AF:

0.000525

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000217

Gnomad OTH exome

AF:

0.000883

GnomAD4 exome

AF:

0.000502

AC:

214

AN:

426438

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

119

AN XY:

221020

show subpopulations

African (AFR)

AF:

0.000682

AC:

AN:

11736

American (AMR)

AF:

0.000915

AC:

AN:

26228

Ashkenazi Jewish (ASJ)

AF:

0.000202

AC:

AN:

9902

East Asian (EAS)

AF:

0.00

AC:

AN:

9900

South Asian (SAS)

AF:

0.000942

AC:

AN:

44588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24326

Middle Eastern (MID)

AF:

0.00510

AC:

AN:

1176

European-Non Finnish (NFE)

AF:

0.000389

AC:

110

AN:

282604

Other (OTH)

AF:

0.00138

AC:

AN:

15978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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

AF:

0.000521

AC:

AN:

51786

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

AN XY:

24778

show subpopulations

African (AFR)

AF:

0.000536

AC:

AN:

13062

American (AMR)

AF:

0.00138

AC:

AN:

3636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1402

East Asian (EAS)

AF:

0.00

AC:

AN:

2004

South Asian (SAS)

AF:

0.00256

AC:

AN:

1564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1970

Middle Eastern (MID)

AF:

0.00909

AC:

AN:

110

European-Non Finnish (NFE)

AF:

0.000371

AC:

AN:

26922

Other (OTH)

AF:

0.00

AC:

AN:

674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000151

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

0.57

Mutation Taster

=42/58

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.82

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