Genetic Variant TNC:c.6496-7_6496-6dupTT (chr9-115021272-T-TAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_002160.4(TNC):c.6496-7_6496-6dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,189,330 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

TNC
NM_002160.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.292

Publications

0 publications found

Variant links:

Genes affected

TNC (HGNC:5318): (tenascin C) This gene encodes an extracellular matrix protein with a spatially and temporally restricted tissue distribution. This protein is homohexameric with disulfide-linked subunits, and contains multiple EGF-like and fibronectin type-III domains. It is implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity, and neuronal regeneration. [provided by RefSeq, Jul 2011]

TNC links:

DELEC1 (HGNC:23658): (deleted in esophageal cancer 1) The function of this gene is not known. This gene is located in a region commonly deleted in esophageal squamous cell carcinomas. Gene expression is reduced or absent in these carcinomas and thus this is a candidate tumor suppressor gene for esophageal squamous cell carcinomas. [provided by RefSeq, Jul 2008]

DELEC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002160.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNC	NM_002160.4	MANE Select	c.6496-7_6496-6dupTT	splice_region intron	N/A	NP_002151.2	P24821-1
TNC	NM_001439065.1		c.7045-7_7045-6dupTT	splice_region intron	N/A	NP_001425994.1
TNC	NM_001439066.1		c.7045-7_7045-6dupTT	splice_region intron	N/A	NP_001425995.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNC	ENST00000350763.9	TSL:1 MANE Select	c.6496-7_6496-6dupTT	splice_region intron	N/A	ENSP00000265131.4	P24821-1
TNC	ENST00000423613.6	TSL:1	c.5677-7_5677-6dupTT	splice_region intron	N/A	ENSP00000411406.2	E9PC84
TNC	ENST00000542877.6	TSL:1	c.5407-7_5407-6dupTT	splice_region intron	N/A	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000679

AC:

AN:

161918

AF XY:

0.0000457

show subpopulations

Gnomad AFR exome

AF:

0.0000944

Gnomad AMR exome

AF:

0.0000511

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000903

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.0000625

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000589

AC:

AN:

1189330

Hom.:

Cov.:

AF XY:

0.0000439

AC XY:

AN XY:

592140

show subpopulations

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

African (AFR)

AF:

0.000122

AC:

AN:

24674

American (AMR)

AF:

0.0000916

AC:

AN:

32738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19920

East Asian (EAS)

AF:

0.0000320

AC:

AN:

31208

South Asian (SAS)

AF:

0.000123

AC:

AN:

65266

European-Finnish (FIN)

AF:

0.0000231

AC:

AN:

43374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4362

European-Non Finnish (NFE)

AF:

0.0000544

AC:

AN:

919338

Other (OTH)

AF:

0.0000826

AC:

AN:

48450

⚠️ 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: 0.243

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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9-115021272-TAAAA-TAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over