chr1-175366276-A-G

Variant names:

• chr1-175366276-A-G
• rs1385540
• NM_003285.3:c.2054-138T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003285.3(TNR):​c.2054-138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNR NM_003285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.2054-138T>C		intron	N/A	NP_003276.3
	TNR	NM_001328635.2		c.1055-138T>C		intron	N/A	NP_001315564.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNR	ENST00000367674.7	TSL:5 MANE Select	c.2054-138T>C		intron	N/A	ENSP00000356646.1
	TNR	ENST00000713954.1		c.2054-138T>C		intron	N/A	ENSP00000519247.1
	TNR	ENST00000713977.1		c.1313-138T>C		intron	N/A	ENSP00000519268.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 734628 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 365818

African (AFR) AF: 0.00 AC: 0 AN: 17452

American (AMR) AF: 0.00 AC: 0 AN: 16084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14646

East Asian (EAS) AF: 0.00 AC: 0 AN: 31088

South Asian (SAS) AF: 0.00 AC: 0 AN: 35770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 543808

Other (OTH) AF: 0.00 AC: 0 AN: 34668

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		0.71

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: rs1385540; hg19: chr1-175335412;