rs140481433
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBS1_SupportingBS2
The NM_003285.3(TNR):āc.1774A>Gā(p.Thr592Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000748 in 1,587,174 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.00027 ( 0 hom., cov: 31)
Exomes š: 0.00080 ( 3 hom. )
Consequence
TNR
NM_003285.3 missense
NM_003285.3 missense
Scores
6
11
2
Clinical Significance
Conservation
PhyloP100: 7.23
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.875
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00027 (41/152068) while in subpopulation NFE AF= 0.000515 (35/68004). AF 95% confidence interval is 0.00038. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNR | NM_003285.3 | c.1774A>G | p.Thr592Ala | missense_variant | 8/23 | ENST00000367674.7 | NP_003276.3 | |
TNR | NM_001328635.2 | c.775A>G | p.Thr259Ala | missense_variant | 8/23 | NP_001315564.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNR | ENST00000367674.7 | c.1774A>G | p.Thr592Ala | missense_variant | 8/23 | 5 | NM_003285.3 | ENSP00000356646 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000270 AC: 41AN: 152068Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
41
AN:
152068
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000186 AC: 44AN: 236948Hom.: 0 AF XY: 0.000156 AC XY: 20AN XY: 128232
GnomAD3 exomes
AF:
AC:
44
AN:
236948
Hom.:
AF XY:
AC XY:
20
AN XY:
128232
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000799 AC: 1146AN: 1435106Hom.: 3 Cov.: 55 AF XY: 0.000735 AC XY: 522AN XY: 710150
GnomAD4 exome
AF:
AC:
1146
AN:
1435106
Hom.:
Cov.:
55
AF XY:
AC XY:
522
AN XY:
710150
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000270 AC: 41AN: 152068Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20AN XY: 74274
GnomAD4 genome
AF:
AC:
41
AN:
152068
Hom.:
Cov.:
31
AF XY:
AC XY:
20
AN XY:
74274
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
7
ALSPAC
AF:
AC:
7
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
8
ExAC
AF:
AC:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2022 | The c.1774A>G (p.T592A) alteration is located in exon 8 (coding exon 6) of the TNR gene. This alteration results from a A to G substitution at nucleotide position 1774, causing the threonine (T) at amino acid position 592 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Parkinson disease Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Jan 01, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at