rs12563833

Positions:

• chr1-175140381-G-A
• chr1-175140381-G-C
• chr1-175140381-G-T

Variant summary

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

The NM_022093.2(TNN):​c.3595+3393G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,970 control chromosomes in the GnomAD database, including 6,423 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 0.28 (6423 hom., cov: 33)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNN	NM_022093.2	c.3595+3393G>A		intron_variant		ENST00000239462.9	NP_071376.1
TNN	XM_017002048.2	c.3649+3393G>A		intron_variant			XP_016857537.1
TNN	XM_017002049.2	c.3385+3393G>A		intron_variant			XP_016857538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNN	ENST00000239462.9	c.3595+3393G>A		intron_variant		2	NM_022093.2	ENSP00000239462	P1
TNN	ENST00000621086.1	c.3064+3393G>A		intron_variant		5		ENSP00000480895

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42186 AN: 151852 Hom.: 6419 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.278 AC: 42206 AN: 151970 Hom.: 6423 Cov.: 33 AF XY: 0.280 AC XY: 20829 AN XY: 74276

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.308

Alfa AF: 0.307 Hom.: 14777

Bravo AF: 0.285

Asia WGS AF: 0.395 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.91

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: rs12563833; hg19: chr1-175109517;