NM_022093.2:c.3596-405T>G

Variant names:

• chr1-175143982-T-G
• rs10489328
• NM_022093.2:c.3596-405T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022093.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNN	NM_022093.2	MANE Select	c.3596-405T>G		intron	N/A	NP_071376.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNN	ENST00000239462.9	TSL:2 MANE Select	c.3596-405T>G		intron	N/A	ENSP00000239462.4
	TNN	ENST00000621086.1	TSL:5	c.3065-405T>G		intron	N/A	ENSP00000480895.1

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

African (AFR) AF: 0.731 AC: 30221 AN: 41342

American (AMR) AF: 0.835 AC: 12749 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2808 AN: 3468

East Asian (EAS) AF: 0.723 AC: 3687 AN: 5100

South Asian (SAS) AF: 0.726 AC: 3463 AN: 4768

European-Finnish (FIN) AF: 0.861 AC: 9064 AN: 10528

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 55953 AN: 67926

Other (OTH) AF: 0.807 AC: 1699 AN: 2106

Alfa AF: 0.808 Hom.: 150438

Bravo AF: 0.790

Asia WGS AF: 0.736 AC: 2559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.47
PhyloP100		-0.56
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: rs10489328; hg19: chr1-175113118;