rs2157588

Variant names:

• chr1-175138690-C-T
• rs2157588
• NM_022093.2:c.3595+1702C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022093.2(TNN):​c.3595+1702C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,036 control chromosomes in the GnomAD database, including 11,053 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 0.37 (11053 hom., cov: 32)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 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.3595+1702C>T		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.3595+1702C>T		intron	N/A	ENSP00000239462.4	Q9UQP3
	TNN	ENST00000860455.1		c.3595+1702C>T		intron	N/A	ENSP00000530514.1
	TNN	ENST00000946425.1		c.3595+1702C>T		intron	N/A	ENSP00000616484.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55831 AN: 151918 Hom.: 11050 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.367 AC: 55844 AN: 152036 Hom.: 11053 Cov.: 32 AF XY: 0.365 AC XY: 27092 AN XY: 74314

African (AFR) AF: 0.272 AC: 11299 AN: 41476

American (AMR) AF: 0.308 AC: 4707 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1018 AN: 3472

East Asian (EAS) AF: 0.0808 AC: 419 AN: 5186

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4810

European-Finnish (FIN) AF: 0.489 AC: 5154 AN: 10550

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 30958 AN: 67960

Other (OTH) AF: 0.361 AC: 763 AN: 2112

Alfa AF: 0.403 Hom.: 16660

Bravo AF: 0.347

Asia WGS AF: 0.198 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.066
DANN	Benign	0.69
PhyloP100		-1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2157588;

hg19: chr1-175107826;

COSMIC: COSV53434212;