1-175457941-A-G

Variant names:

• chr1-175457941-A-G
• rs863516
• NM_003285.3:c.-63-51164T>C

Variant summary

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

The NM_003285.3(TNR):​c.-63-51164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 152,360 control chromosomes in the GnomAD database, including 73,446 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 0.98 (73446 hom., cov: 33)
• Consequence: TNR NM_003285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 2 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNR	NM_003285.3	MANE Select	c.-63-51164T>C		intron	N/A	NP_003276.3
	TNR	NM_001328635.2		c.-958-51164T>C		intron	N/A	NP_001315564.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNR	ENST00000367674.7	TSL:5 MANE Select	c.-63-51164T>C		intron	N/A	ENSP00000356646.1	Q92752-1
	TNR	ENST00000713977.1		c.-63-51164T>C		intron	N/A	ENSP00000519268.1	A0AAQ5BHB2
	TNR	ENST00000713978.1		n.-63-51164T>C		intron	N/A	ENSP00000519269.1	A0AAQ5BH84

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149468 AN: 152242 Hom.: 73388 Cov.: 33

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 0.987

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.988

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

GnomAD4 genome AF: 0.982 AC: 149585 AN: 152360 Hom.: 73446 Cov.: 33 AF XY: 0.983 AC XY: 73221 AN XY: 74512

African (AFR) AF: 0.995 AC: 41352 AN: 41580

American (AMR) AF: 0.987 AC: 15111 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.987 AC: 3426 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5181 AN: 5182

South Asian (SAS) AF: 0.994 AC: 4803 AN: 4830

European-Finnish (FIN) AF: 0.976 AC: 10369 AN: 10628

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 66053 AN: 68042

Other (OTH) AF: 0.988 AC: 2089 AN: 2114

Alfa AF: 0.979 Hom.: 9245

Bravo AF: 0.983

Asia WGS AF: 0.997 AC: 3468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		1.6
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: rs863516; hg19: chr1-175427077;