rs6681984

Variant names:

• chr1-175088986-C-T
• rs6681984
• NM_022093.2:c.1324+3492C>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.1324+3492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,000 control chromosomes in the GnomAD database, including 23,491 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 0.55 (23491 hom., cov: 33)
• Consequence: TNN NM_022093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNN	NM_022093.2	c.1324+3492C>T		intron_variant	Intron 6 of 18	ENST00000239462.9	NP_071376.1
TNN	XM_017002048.2	c.1378+3492C>T		intron_variant	Intron 6 of 18		XP_016857537.1
TNN	XM_017002049.2	c.1378+3492C>T		intron_variant	Intron 6 of 17		XP_016857538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNN	ENST00000239462.9	c.1324+3492C>T		intron_variant	Intron 6 of 18	2	NM_022093.2	ENSP00000239462.4
TNN	ENST00000621086.1	c.1324+3492C>T		intron_variant	Intron 5 of 15	5		ENSP00000480895.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83330 AN: 151882 Hom.: 23451 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.549 AC: 83431 AN: 152000 Hom.: 23491 Cov.: 33 AF XY: 0.545 AC XY: 40452 AN XY: 74278

African (AFR) AF: 0.689 AC: 28577 AN: 41460

American (AMR) AF: 0.481 AC: 7342 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1980 AN: 5164

South Asian (SAS) AF: 0.492 AC: 2375 AN: 4824

European-Finnish (FIN) AF: 0.504 AC: 5311 AN: 10534

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34426 AN: 67968

Other (OTH) AF: 0.554 AC: 1171 AN: 2112

Alfa AF: 0.535 Hom.: 3858

Bravo AF: 0.554

Asia WGS AF: 0.501 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.15
PhyloP100		0.36
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: rs6681984; hg19: chr1-175058122;