rs12065394

Variant names:

• chr1-175070467-T-C
• rs12065394
• NM_022093.2:c.-36+2532T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNN	NM_022093.2	c.-36+2532T>C		intron_variant	Intron 1 of 18	ENST00000239462.9	NP_071376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNN	ENST00000239462.9	c.-36+2532T>C		intron_variant	Intron 1 of 18	2	NM_022093.2	ENSP00000239462.4

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

African (AFR) AF: 0.166 AC: 6869 AN: 41468

American (AMR) AF: 0.124 AC: 1892 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3470

East Asian (EAS) AF: 0.0614 AC: 317 AN: 5160

South Asian (SAS) AF: 0.131 AC: 629 AN: 4802

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10578

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12837 AN: 67962

Other (OTH) AF: 0.165 AC: 349 AN: 2112

Alfa AF: 0.177 Hom.: 515

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
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12065394; hg19: chr1-175039603;