1-175379587-C-T

Variant names:

• chr1-175379587-C-T
• rs859427
• NM_003285.3:c.1928G>A

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNR	NM_003285.3	c.1928G>A	p.Arg643Lys	missense_variant	Exon 9 of 23	ENST00000367674.7	NP_003276.3
TNR	NM_001328635.2	c.929G>A	p.Arg310Lys	missense_variant	Exon 9 of 23		NP_001315564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNR	ENST00000367674.7	c.1928G>A	p.Arg643Lys	missense_variant	Exon 9 of 23	5	NM_003285.3	ENSP00000356646.1

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

GnomAD3 exomes AF: 0.675 AC: 169575 AN: 251122 Hom.: 57773 AF XY: 0.671 AC XY: 90994 AN XY: 135698

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 SAS exome AF: 0.673

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

Gnomad4 AFR exome AF: 0.660

Gnomad4 AMR exome AF: 0.751

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.802

Gnomad4 SAS exome AF: 0.672

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.654

Gnomad4 OTH exome AF: 0.656

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

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.648

Alfa AF: 0.662 Hom.: 82420

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 v4.3

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;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;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.67	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.91	N;N
REVEL	Benign	0.050
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.016
MPC		0.21
ClinPred		0.0034	T
GERP RS		2.8
Varity_R		0.037
gMVP		0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs859427; hg19: chr1-175348723; COSMIC: COSV54903706;