chr7-5308872-T-A

Variant names:

• chr7-5308872-T-A
• rs560820937
• NM_001080495.3:c.8700+3A>T

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>T 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 0.000019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000054 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNRC18 NM_001080495.3 splice_region, intron
• Scores: Splicing: ADA: 0.9962
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572
• Publications: 0 publications found

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]

ACMG classification

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

Frequencies

GnomAD3 genomes AF: 0.0000193 AC: 1 AN: 51752 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000767

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000540 AC: 23 AN: 425974 Hom.: 0 Cov.: 28 AF XY: 0.0000589 AC XY: 13 AN XY: 220816

African (AFR) AF: 0.00 AC: 0 AN: 11724

American (AMR) AF: 0.00 AC: 0 AN: 26228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9900

East Asian (EAS) AF: 0.00 AC: 0 AN: 9894

South Asian (SAS) AF: 0.00 AC: 0 AN: 44582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1174

European-Non Finnish (NFE) AF: 0.0000815 AC: 23 AN: 282190

Other (OTH) AF: 0.00 AC: 0 AN: 15958

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000193 AC: 1 AN: 51776 Hom.: 0 Cov.: 0 AF XY: 0.0000404 AC XY: 1 AN XY: 24772

African (AFR) AF: 0.0000766 AC: 1 AN: 13058

American (AMR) AF: 0.00 AC: 0 AN: 3632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1402

East Asian (EAS) AF: 0.00 AC: 0 AN: 2004

South Asian (SAS) AF: 0.00 AC: 0 AN: 1564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26920

Other (OTH) AF: 0.00 AC: 0 AN: 674

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.90
PhyloP100		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.88
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

Other links and lift over

dbSNP: rs560820937; hg19: chr7-5348503;