rs10798333

Variant names:

• chr1-175123571-C-T
• rs10798333
• NM_022093.2:c.2822C>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.2822C>T​(p.Thr941Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,613,816 control chromosomes in the GnomAD database, including 132,464 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11793 hom., cov: 32)
  • Exomes 𝑓: 0.40 (120671 hom.)
• Consequence: TNN NM_022093.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 25 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 (MetaRNN=0.0012792051).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNN	NM_022093.2	c.2822C>T	p.Thr941Met	missense_variant	Exon 12 of 19	ENST00000239462.9	NP_071376.1
TNN	XM_017002048.2	c.2876C>T	p.Thr959Met	missense_variant	Exon 12 of 19		XP_016857537.1
TNN	XM_017002049.2	c.2612C>T	p.Thr871Met	missense_variant	Exon 11 of 18		XP_016857538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNN	ENST00000239462.9	c.2822C>T	p.Thr941Met	missense_variant	Exon 12 of 19	2	NM_022093.2	ENSP00000239462.4
TNN	ENST00000621086.1	c.2291C>T	p.Thr764Met	missense_variant	Exon 9 of 16	5		ENSP00000480895.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58711 AN: 151866 Hom.: 11785 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0882

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.366

GnomAD2 exomes AF: 0.337 AC: 84767 AN: 251392 AF XY: 0.337

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.0862

Gnomad FIN exome AF: 0.458

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.363

GnomAD4 exome AF: 0.397 AC: 580440 AN: 1461832 Hom.: 120671 Cov.: 80 AF XY: 0.392 AC XY: 285063 AN XY: 727216

African (AFR) AF: 0.409 AC: 13691 AN: 33480

American (AMR) AF: 0.226 AC: 10112 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 7045 AN: 26134

East Asian (EAS) AF: 0.0891 AC: 3536 AN: 39700

South Asian (SAS) AF: 0.224 AC: 19339 AN: 86256

European-Finnish (FIN) AF: 0.452 AC: 24166 AN: 53412

Middle Eastern (MID) AF: 0.306 AC: 1764 AN: 5766

European-Non Finnish (NFE) AF: 0.430 AC: 478218 AN: 1111972

Other (OTH) AF: 0.374 AC: 22569 AN: 60392

GnomAD4 genome AF: 0.387 AC: 58751 AN: 151984 Hom.: 11793 Cov.: 32 AF XY: 0.382 AC XY: 28405 AN XY: 74298

African (AFR) AF: 0.405 AC: 16769 AN: 41450

American (AMR) AF: 0.296 AC: 4525 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 931 AN: 3470

East Asian (EAS) AF: 0.0882 AC: 455 AN: 5156

South Asian (SAS) AF: 0.213 AC: 1026 AN: 4822

European-Finnish (FIN) AF: 0.466 AC: 4929 AN: 10570

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28957 AN: 67936

Other (OTH) AF: 0.367 AC: 775 AN: 2110

Alfa AF: 0.393 Hom.: 20100

Bravo AF: 0.373

TwinsUK AF: 0.458 AC: 1697

ALSPAC AF: 0.423 AC: 1631

ESP6500AA AF: 0.403 AC: 1776

ESP6500EA AF: 0.418 AC: 3593

ExAC AF: 0.343 AC: 41616

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.71	T;T;T
MetaRNN	Benign	0.0013	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M;.;.
PhyloP100		0.13
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D;.;.
REVEL	Benign	0.14
Sift	Benign	0.034	D;.;.
Sift4G	Benign	0.13	T;T;T
Polyphen		0.54	P;.;.
Vest4		0.13
MPC		0.12
ClinPred		0.048	T
GERP RS		3.1
Varity_R		0.087
gMVP		0.28
Mutation Taster		=95/5	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: rs10798333; hg19: chr1-175092707; COSMIC: COSV53431636;