chr1-175379587-C-A

Position:

• chr1-175379587-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R643K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TNR NM_003285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNR	NM_003285.3	c.1928G>T	p.Arg643Met	missense_variant	9/23	ENST00000367674.7	NP_003276.3
TNR	NM_001328635.2	c.929G>T	p.Arg310Met	missense_variant	9/23		NP_001315564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNR	ENST00000367674.7	c.1928G>T	p.Arg643Met	missense_variant	9/23	5	NM_003285.3	ENSP00000356646.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;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;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.067	T;T
Polyphen		0.59	P;P
Vest4		0.30
MutPred		0.63		Gain of catalytic residue at V639 (P = 0.0117);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs859427; hg19: chr1-175348723;