Variant 1-175337622-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.14

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 1487 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNR	ENST00000367674.7 linkuse as main transcript	c.3440C>T	p.Thr1147Ile	missense_variant	19/23	5	NM_003285.3	P1	Q92752-1

Frequencies

GnomAD3 genomes

AF:

0.00974

AC:

1482

AN:

152224

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00190

AC XY:

258

AN XY:

135784

show subpopulations

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.:

Cov.:

AF XY:

0.00108

AC XY:

783

AN XY:

727236

show subpopulations

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.:

Cov.:

AF XY:

0.00963

AC XY:

717

AN XY:

74488

show subpopulations

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.:

Bravo

AF:

0.0111

ESP6500AA

AF:

0.0311

AC:

137

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00299

AC:

363

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

.;T

MetaRNN

Benign

0.0097

T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over