rs859427

Variant names:

• chr1-175379587-C-A
• rs859427
• NM_003285.3:c.1928G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-175379587-C-A
• chr1-175379587-C-G
• chr1-175379587-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003285.3(TNR):​c.1928G>T​(p.Arg643Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 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: not found (cov: 31)
• Consequence: TNR NM_003285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 28 publications found

Genes affected

TNR (HGNC:11953): (tenascin R) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The encoded protein is restricted to the central nervous system. The protein may play a role in neurite outgrowth, neural cell adhesion and modulation of sodium channel function. It is a constituent of perineuronal nets. [provided by RefSeq, Aug 2013]

TNR Gene-Disease associations (from GenCC):

• neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003285.3. 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
	TNR	NM_003285.3	MANE Select	c.1928G>T	p.Arg643Met	missense	Exon 9 of 23	NP_003276.3
	TNR	NM_001328635.2		c.929G>T	p.Arg310Met	missense	Exon 9 of 23	NP_001315564.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNR	ENST00000367674.7	TSL:5 MANE Select	c.1928G>T	p.Arg643Met	missense	Exon 9 of 23	ENSP00000356646.1
	TNR	ENST00000713954.1		c.1928G>T	p.Arg643Met	missense	Exon 7 of 20	ENSP00000519247.1
	TNR	ENST00000713977.1		c.1187G>T	p.Arg396Met	missense	Exon 6 of 20	ENSP00000519268.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		2.2
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.27
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.067	T
Polyphen		0.59	P
Vest4		0.30
MutPred		0.63		Gain of catalytic residue at V639 (P = 0.0117)
MVP		0.58
MPC		0.77
ClinPred		0.95	D
GERP RS		2.8
Varity_R		0.089
gMVP		0.55
Mutation Taster		=79/21	polymorphism

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: rs859427; hg19: chr1-175348723;