1-175143982-T-G

Variant summary

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

The NM_022093.2(TNN):c.3596-405T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 151,708 control chromosomes in the GnomAD database, including 48,106 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 0.79 (48106 hom., cov: 28)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNN	NM_022093.2	c.3596-405T>G		intron_variant		ENST00000239462.9
TNN	XM_017002048.2	c.3650-405T>G		intron_variant
TNN	XM_017002049.2	c.3386-405T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNN	ENST00000239462.9	c.3596-405T>G		intron_variant		2	NM_022093.2	P1
TNN	ENST00000621086.1	c.3065-405T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120530 AN: 151590 Hom.: 48083 Cov.: 28

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.795 AC: 120599 AN: 151708 Hom.: 48106 Cov.: 28 AF XY: 0.797 AC XY: 59072 AN XY: 74132

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.807

Alfa AF: 0.812 Hom.: 98069

Bravo AF: 0.790

Asia WGS AF: 0.736 AC: 2559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.54
Dann	Benign	0.47

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: rs10489328; hg19: chr1-175113118;