9-115021272-TAAAA-TAAAAAAA

Variant names:

• chr9-115021272-T-TAAA
• rs5900112
• NM_002160.4:c.6496-8_6496-6dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002160.4(TNC):​c.6496-8_6496-6dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,189,990 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: not found (cov: 24)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: TNC NM_002160.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.6496-8_6496-6dupTTT		splice_region intron	N/A	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.7045-8_7045-6dupTTT		splice_region intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.7045-8_7045-6dupTTT		splice_region intron	N/A	NP_001425995.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.6496-8_6496-6dupTTT		splice_region intron	N/A	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.5677-8_5677-6dupTTT		splice_region intron	N/A	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.5407-8_5407-6dupTTT		splice_region intron	N/A	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000252 AC: 3 AN: 1189990 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 592474

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

African (AFR) AF: 0.00 AC: 0 AN: 24692

American (AMR) AF: 0.0000305 AC: 1 AN: 32756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19930

East Asian (EAS) AF: 0.00 AC: 0 AN: 31220

South Asian (SAS) AF: 0.00 AC: 0 AN: 65330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4364

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 919818

Other (OTH) AF: 0.00 AC: 0 AN: 48484

⚠️ 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.

GnomAD4 genome Cov.: 24

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

Other links and lift over

dbSNP: rs5900112; hg19: chr9-117783551;