1-175330113-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003285.3(TNR):c.3754C>T(p.Leu1252=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,611,056 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (20 hom.)
• Consequence: TNR NM_003285.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.38

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-175330113-G-A is Benign according to our data. Variant chr1-175330113-G-A is described in ClinVar as [Benign]. Clinvar id is 708860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-175330113-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.38 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00247 (377/152372) while in subpopulation NFE AF= 0.00341 (232/68032). AF 95% confidence interval is 0.00305. There are 2 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 377 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNR	NM_003285.3	c.3754C>T	p.Leu1252=	synonymous_variant	21/23	ENST00000367674.7
LOC105371623	XR_001738299.2	n.318+603G>A		intron_variant, non_coding_transcript_variant
TNR	NM_001328635.2	c.2755C>T	p.Leu919=	synonymous_variant	21/23
LOC105371623	XR_001738302.2	n.232-3209G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNR	ENST00000367674.7	c.3754C>T	p.Leu1252=	synonymous_variant	21/23	5	NM_003285.3	P1
	ENST00000569593.1	n.336-264G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00248 AC: 377 AN: 152254 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00341

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00313 AC: 784 AN: 250556 Hom.: 2 AF XY: 0.00300 AC XY: 406 AN XY: 135380

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00319

Gnomad ASJ exome AF: 0.0189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00354

Gnomad OTH exome AF: 0.00639

GnomAD4 exome AF: 0.00336 AC: 4894 AN: 1458684 Hom.: 20 Cov.: 29 AF XY: 0.00325 AC XY: 2353 AN XY: 725016

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00336

Gnomad4 ASJ exome AF: 0.0183

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00127

Gnomad4 NFE exome AF: 0.00342

Gnomad4 OTH exome AF: 0.00445

GnomAD4 genome AF: 0.00247 AC: 377 AN: 152372 Hom.: 2 Cov.: 33 AF XY: 0.00203 AC XY: 151 AN XY: 74518

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00341

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00430 Hom.: 0

Bravo AF: 0.00261

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00398

EpiControl AF: 0.00404

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	TNR: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	5.9
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs35421365; hg19: chr1-175299249;