rs2228359

Variant names:

• chr1-175355515-A-G
• rs2228359
• NM_003285.3:c.3237T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-175355515-A-G
• chr1-175355515-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003285.3(TNR):​c.3237T>C​(p.Asp1079Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,613,486 control chromosomes in the GnomAD database, including 383,955 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 0.65 (32655 hom., cov: 32)
  • Exomes 𝑓: 0.69 (351300 hom.)
• Consequence: TNR NM_003285.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951
• Publications: 19 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.951 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNR	NM_003285.3	c.3237T>C	p.Asp1079Asp	synonymous_variant	Exon 17 of 23	ENST00000367674.7	NP_003276.3
TNR	NM_001328635.2	c.2238T>C	p.Asp746Asp	synonymous_variant	Exon 17 of 23		NP_001315564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNR	ENST00000367674.7	c.3237T>C	p.Asp1079Asp	synonymous_variant	Exon 17 of 23	5	NM_003285.3	ENSP00000356646.1
TNR	ENST00000713954.1	c.3237T>C	p.Asp1079Asp	synonymous_variant	Exon 15 of 20			ENSP00000519247.1
TNR	ENST00000713977.1	c.2496T>C	p.Asp832Asp	synonymous_variant	Exon 14 of 20			ENSP00000519268.1
TNR	ENST00000713955.1	n.3237T>C		non_coding_transcript_exon_variant	Exon 15 of 21			ENSP00000519248.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98752 AN: 151938 Hom.: 32628 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.638

GnomAD2 exomes AF: 0.697 AC: 174673 AN: 250766 AF XY: 0.695

Gnomad AFR exome AF: 0.536

Gnomad AMR exome AF: 0.756

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.816

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.684

Gnomad OTH exome AF: 0.685

GnomAD4 exome AF: 0.692 AC: 1011000 AN: 1461430 Hom.: 351300 Cov.: 57 AF XY: 0.691 AC XY: 502577 AN XY: 726998

African (AFR) AF: 0.527 AC: 17638 AN: 33462

American (AMR) AF: 0.747 AC: 33409 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 17229 AN: 26122

East Asian (EAS) AF: 0.837 AC: 33220 AN: 39688

South Asian (SAS) AF: 0.682 AC: 58789 AN: 86204

European-Finnish (FIN) AF: 0.723 AC: 38619 AN: 53396

Middle Eastern (MID) AF: 0.642 AC: 3698 AN: 5762

European-Non Finnish (NFE) AF: 0.690 AC: 767140 AN: 1111734

Other (OTH) AF: 0.683 AC: 41258 AN: 60366

GnomAD4 genome AF: 0.650 AC: 98828 AN: 152056 Hom.: 32655 Cov.: 32 AF XY: 0.655 AC XY: 48677 AN XY: 74328

African (AFR) AF: 0.529 AC: 21937 AN: 41436

American (AMR) AF: 0.712 AC: 10877 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2287 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4175 AN: 5176

South Asian (SAS) AF: 0.675 AC: 3257 AN: 4828

European-Finnish (FIN) AF: 0.723 AC: 7642 AN: 10564

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46594 AN: 67998

Other (OTH) AF: 0.643 AC: 1355 AN: 2108

Alfa AF: 0.672 Hom.: 49944

Bravo AF: 0.644

Asia WGS AF: 0.721 AC: 2508 AN: 3478

EpiCase AF: 0.669

EpiControl AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.68
DANN	Benign	0.46
PhyloP100		0.95
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: rs2228359; hg19: chr1-175324651; COSMIC: COSV54901946;