1-175330143-C-G

Variant names:

• chr1-175330143-C-G
• NM_003285.3:c.3724G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003285.3(TNR):​c.3724G>C​(p.Asp1242His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNR NM_003285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03

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]

ENSG00000260990 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNR	NM_003285.3	c.3724G>C	p.Asp1242His	missense_variant	Exon 21 of 23	ENST00000367674.7	NP_003276.3
TNR	NM_001328635.2	c.2725G>C	p.Asp909His	missense_variant	Exon 21 of 23		NP_001315564.1
LOC105371623	XR_001738299.2	n.318+633C>G		intron_variant	Intron 3 of 4
LOC105371623	XR_001738302.2	n.232-3179C>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNR	ENST00000367674.7	c.3724G>C	p.Asp1242His	missense_variant	Exon 21 of 23	5	NM_003285.3	ENSP00000356646.1
ENSG00000260990	ENST00000569593.1	n.336-234C>G		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TNR: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.3	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.72
MutPred		0.64		Gain of catalytic residue at D1242 (P = 0.0688);Gain of catalytic residue at D1242 (P = 0.0688);
MVP		0.50
MPC		2.0
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.77
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-175299279;