rs12037583

Variant names:

• chr1-175624169-C-T
• rs12037583
• NM_003285.3:c.-164-95800G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003285.3(TNR):​c.-164-95800G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 152,214 control chromosomes in the GnomAD database, including 922 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 0.085 (922 hom., cov: 32)
• Consequence: TNR NM_003285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNR	NM_003285.3	c.-164-95800G>A		intron_variant	Intron 1 of 22	ENST00000367674.7	NP_003276.3
TNR	NM_001328635.2	c.-1059-95800G>A		intron_variant	Intron 1 of 22		NP_001315564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNR	ENST00000367674.7	c.-164-95800G>A		intron_variant	Intron 1 of 22	5	NM_003285.3	ENSP00000356646.1

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 12914 AN: 152094 Hom.: 921 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.0884

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

GnomAD4 genome AF: 0.0848 AC: 12909 AN: 152214 Hom.: 922 Cov.: 32 AF XY: 0.0881 AC XY: 6557 AN XY: 74422

African (AFR) AF: 0.0180 AC: 746 AN: 41550

American (AMR) AF: 0.0702 AC: 1073 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1958 AN: 5152

South Asian (SAS) AF: 0.146 AC: 704 AN: 4820

European-Finnish (FIN) AF: 0.108 AC: 1150 AN: 10604

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0960 AC: 6526 AN: 68006

Other (OTH) AF: 0.0880 AC: 186 AN: 2114

Alfa AF: 0.0941 Hom.: 1304

Bravo AF: 0.0796

Asia WGS AF: 0.222 AC: 768 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.87
DANN	Benign	0.27
PhyloP100		-0.029
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: rs12037583; hg19: chr1-175593305;