Genetic Variant NM_002160.4:c.6496-20_6496-17dupCTCT (chr9-115021283-A-AAGAG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002160.4(TNC):c.6496-20_6496-17dupCTCT variant causes a intron change. The variant allele was found at a frequency of 0.000121 in 1,102,038 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TNC
NM_002160.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.13

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 24 AD gene.

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.6496-20_6496-17dupCTCT	intron	N/A	NP_002151.2	P24821-1
TNC	NM_001439065.1		c.7045-20_7045-17dupCTCT	intron	N/A	NP_001425994.1
TNC	NM_001439066.1		c.7045-20_7045-17dupCTCT	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.6496-20_6496-17dupCTCT	intron	N/A	ENSP00000265131.4	P24821-1
TNC	ENST00000423613.6	TSL:1	c.5677-20_5677-17dupCTCT	intron	N/A	ENSP00000411406.2	E9PC84
TNC	ENST00000542877.6	TSL:1	c.5407-20_5407-17dupCTCT	intron	N/A	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes

AF:

0.000174

AC:

AN:

149626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000779

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000104

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000114

AC:

109

AN:

952306

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

474176

show subpopulations

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

African (AFR)

AF:

0.000556

AC:

AN:

23362

American (AMR)

AF:

0.000321

AC:

AN:

28060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16852

East Asian (EAS)

AF:

0.00

AC:

AN:

27362

South Asian (SAS)

AF:

0.0000875

AC:

AN:

57132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3850

European-Non Finnish (NFE)

AF:

0.000110

AC:

AN:

725140

Other (OTH)

AF:

0.0000511

AC:

AN:

39146

⚠️ 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: 0.348

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:

0.000160

AC:

AN:

149732

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

73060

show subpopulations

African (AFR)

AF:

0.000294

AC:

AN:

40792

American (AMR)

AF:

0.000133

AC:

AN:

15010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.000391

AC:

AN:

5120

South Asian (SAS)

AF:

0.000213

AC:

AN:

4696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

67292

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.1

Splicing

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

Publications

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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