chr1-175379587-C-T

Variant names:

• chr1-175379587-C-T
• rs859427
• NM_003285.3:c.1928G>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.1928G>A​(p.Arg643Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,613,402 control chromosomes in the GnomAD database, including 353,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (33556 hom., cov: 31)
  • Exomes 𝑓: 0.66 (319539 hom.)
• Consequence: TNR NM_003285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 28 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 (MetaRNN=9.2071866E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 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.1928G>A	p.Arg643Lys	missense	Exon 9 of 23	NP_003276.3
	TNR	NM_001328635.2		c.929G>A	p.Arg310Lys	missense	Exon 9 of 23	NP_001315564.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNR	ENST00000367674.7	TSL:5 MANE Select	c.1928G>A	p.Arg643Lys	missense	Exon 9 of 23	ENSP00000356646.1	Q92752-1
	TNR	ENST00000713954.1		c.1928G>A	p.Arg643Lys	missense	Exon 7 of 20	ENSP00000519247.1	A0AAQ5BH57
	TNR	ENST00000713977.1		c.1187G>A	p.Arg396Lys	missense	Exon 6 of 20	ENSP00000519268.1	A0AAQ5BHB2

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100683 AN: 151850 Hom.: 33526 Cov.: 31

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.648

GnomAD2 exomes AF: 0.675 AC: 169575 AN: 251122 AF XY: 0.671

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.758

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.826

Gnomad FIN exome AF: 0.607

Gnomad NFE exome AF: 0.649

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.660 AC: 964568 AN: 1461432 Hom.: 319539 Cov.: 53 AF XY: 0.660 AC XY: 479634 AN XY: 726998

African (AFR) AF: 0.660 AC: 22095 AN: 33464

American (AMR) AF: 0.751 AC: 33587 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 16011 AN: 26130

East Asian (EAS) AF: 0.802 AC: 31822 AN: 39698

South Asian (SAS) AF: 0.672 AC: 57960 AN: 86226

European-Finnish (FIN) AF: 0.608 AC: 32491 AN: 53408

Middle Eastern (MID) AF: 0.669 AC: 3729 AN: 5578

European-Non Finnish (NFE) AF: 0.654 AC: 727273 AN: 1111860

Other (OTH) AF: 0.656 AC: 39600 AN: 60360

GnomAD4 genome AF: 0.663 AC: 100767 AN: 151970 Hom.: 33556 Cov.: 31 AF XY: 0.662 AC XY: 49188 AN XY: 74270

African (AFR) AF: 0.663 AC: 27456 AN: 41426

American (AMR) AF: 0.693 AC: 10583 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3466

East Asian (EAS) AF: 0.817 AC: 4207 AN: 5152

South Asian (SAS) AF: 0.685 AC: 3295 AN: 4812

European-Finnish (FIN) AF: 0.610 AC: 6438 AN: 10556

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44497 AN: 67966

Other (OTH) AF: 0.648 AC: 1368 AN: 2110

Alfa AF: 0.662 Hom.: 113248

Bravo AF: 0.674

TwinsUK AF: 0.655 AC: 2430

ALSPAC AF: 0.651 AC: 2508

ESP6500AA AF: 0.677 AC: 2984

ESP6500EA AF: 0.654 AC: 5627

ExAC AF: 0.673 AC: 81660

Asia WGS AF: 0.707 AC: 2460 AN: 3478

EpiCase AF: 0.655

EpiControl AF: 0.654

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.55
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	9.2e-7	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.67	N
PhyloP100		2.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.91	N
REVEL	Benign	0.050
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.21
ClinPred		0.0034	T
GERP RS		2.8
Varity_R		0.037
gMVP		0.36
Mutation Taster		=94/6	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: rs859427; hg19: chr1-175348723; COSMIC: COSV54903706;