NM_022093.2:c.2650+2134A>G

Variant names:

• chr1-175120958-A-G
• rs6701127
• NM_022093.2:c.2650+2134A>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.2650+2134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,856 control chromosomes in the GnomAD database, including 17,914 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 0.48 (17914 hom., cov: 32)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 3 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNN	NM_022093.2	MANE Select	c.2650+2134A>G		intron	N/A	NP_071376.1	Q9UQP3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNN	ENST00000239462.9	TSL:2 MANE Select	c.2650+2134A>G		intron	N/A	ENSP00000239462.4	Q9UQP3
	TNN	ENST00000860455.1		c.2650+2134A>G		intron	N/A	ENSP00000530514.1
	TNN	ENST00000946425.1		c.2650+2134A>G		intron	N/A	ENSP00000616484.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73129 AN: 151736 Hom.: 17893 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.482 AC: 73189 AN: 151856 Hom.: 17914 Cov.: 32 AF XY: 0.490 AC XY: 36375 AN XY: 74250

African (AFR) AF: 0.455 AC: 18825 AN: 41382

American (AMR) AF: 0.602 AC: 9184 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1838 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3429 AN: 5168

South Asian (SAS) AF: 0.535 AC: 2574 AN: 4810

European-Finnish (FIN) AF: 0.510 AC: 5384 AN: 10554

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30319 AN: 67902

Other (OTH) AF: 0.498 AC: 1051 AN: 2112

Alfa AF: 0.464 Hom.: 21523

Bravo AF: 0.487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.11
PhyloP100		-1.7
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: rs6701127; hg19: chr1-175090094;