rs12065394

chr1-175070467-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022093.2(TNN):c.-36+2532T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,026 control chromosomes in the GnomAD database, including 2,247 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2247 hom., cov: 32)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12

Genes affected

TNN (HGNC:22942): (tenascin N) Predicted to enable integrin binding activity. Predicted to be involved in several processes, including generation of neurons; negative regulation of canonical Wnt signaling pathway involved in osteoblast differentiation; and negative regulation of osteoblast differentiation. Predicted to act upstream of or within axonogenesis. Predicted to be located in extracellular matrix and neuron projection. Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNN	NM_022093.2	c.-36+2532T>C		intron_variant		ENST00000239462.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNN	ENST00000239462.9	c.-36+2532T>C		intron_variant		2	NM_022093.2	P1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25680 AN: 151908 Hom.: 2244 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25693 AN: 152026 Hom.: 2247 Cov.: 32 AF XY: 0.168 AC XY: 12469 AN XY: 74316

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0614

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.165

Alfa AF: 0.177 Hom.: 502

Bravo AF: 0.163

Asia WGS AF: 0.0950 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0060
Dann	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs12065394; hg19: chr1-175039603;