1-175337622-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003285.3(TNR):c.3440C>T(p.Thr1147Ile) variant causes a missense change. The variant allele was found at a frequency of 0.002 in 1,614,204 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (28 hom.)
• Consequence: TNR NM_003285.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.14

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0096844435).
• BP6: Variant 1-175337622-G-A is Benign according to our data. Variant chr1-175337622-G-A is described in ClinVar as [Benign]. Clinvar id is 770496.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00976 (1487/152342) while in subpopulation AFR AF= 0.0331 (1375/41562). AF 95% confidence interval is 0.0316. There are 18 homozygotes in gnomad4. There are 717 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1482 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNR	NM_003285.3	c.3440C>T	p.Thr1147Ile	missense_variant	19/23	ENST00000367674.7
TNR	NM_001328635.2	c.2441C>T	p.Thr814Ile	missense_variant	19/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNR	ENST00000367674.7	c.3440C>T	p.Thr1147Ile	missense_variant	19/23	5	NM_003285.3	P1

Frequencies

GnomAD3 genomes AF: 0.00974 AC: 1482 AN: 152224 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00536

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00252 AC: 633 AN: 251238 Hom.: 8 AF XY: 0.00190 AC XY: 258 AN XY: 135784

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00119 AC: 1745 AN: 1461862 Hom.: 28 Cov.: 31 AF XY: 0.00108 AC XY: 783 AN XY: 727236

Gnomad4 AFR exome AF: 0.0361

Gnomad4 AMR exome AF: 0.00266

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000196

Gnomad4 OTH exome AF: 0.00267

GnomAD4 genome AF: 0.00976 AC: 1487 AN: 152342 Hom.: 18 Cov.: 33 AF XY: 0.00963 AC XY: 717 AN XY: 74488

Gnomad4 AFR AF: 0.0331

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00182 Hom.: 7

Bravo AF: 0.0111

ESP6500AA AF: 0.0311 AC: 137

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00299 AC: 363

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.17
Cadd	Benign	23
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.29	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
MetaRNN	Benign	0.0097	T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.92	P;P
Vest4		0.76
MVP		0.50
MPC		1.6
ClinPred		0.051	T
GERP RS		5.4
Varity_R		0.44
gMVP		0.67

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: rs61731114; hg19: chr1-175306758; COSMIC: COSV54874827; COSMIC: COSV54874827;