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GeneBe

1-175324434-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003285.3(TNR):c.3879G>A(p.Ser1293=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,112 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0079 ( 15 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 10 hom. )

Consequence

TNR
NM_003285.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-175324434-C-T is Benign according to our data. Variant chr1-175324434-C-T is described in ClinVar as [Benign]. Clinvar id is 711296.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.6 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0079 (1202/152240) while in subpopulation AFR AF= 0.0253 (1050/41534). AF 95% confidence interval is 0.024. There are 15 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1193 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNRNM_003285.3 linkuse as main transcriptc.3879G>A p.Ser1293= synonymous_variant 22/23 ENST00000367674.7
LOC105371623XR_001738299.2 linkuse as main transcriptn.231+3313C>T intron_variant, non_coding_transcript_variant
TNRNM_001328635.2 linkuse as main transcriptc.2880G>A p.Ser960= synonymous_variant 22/23
LOC105371623XR_001738302.2 linkuse as main transcriptn.231+3313C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNRENST00000367674.7 linkuse as main transcriptc.3879G>A p.Ser1293= synonymous_variant 22/235 NM_003285.3 P1Q92752-1
ENST00000569593.1 linkuse as main transcriptn.335+3313C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00784
AC:
1193
AN:
152122
Hom.:
14
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0251
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00615
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000573
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00282
AC:
710
AN:
251396
Hom.:
5
AF XY:
0.00226
AC XY:
307
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.0286
Gnomad AMR exome
AF:
0.00373
Gnomad ASJ exome
AF:
0.00268
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000624
Gnomad OTH exome
AF:
0.00277
GnomAD4 exome
AF:
0.00127
AC:
1859
AN:
1461872
Hom.:
10
Cov.:
31
AF XY:
0.00116
AC XY:
841
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0251
Gnomad4 AMR exome
AF:
0.00378
Gnomad4 ASJ exome
AF:
0.00230
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000525
Gnomad4 OTH exome
AF:
0.00295
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00790
AC:
1202
AN:
152240
Hom.:
15
Cov.:
32
AF XY:
0.00766
AC XY:
570
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0253
Gnomad4 AMR
AF:
0.00615
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.000573
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00344
Hom.:
1
Bravo
AF:
0.00904
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000763
EpiControl
AF:
0.00119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
Cadd
Benign
0.95
Dann
Benign
0.85

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.

Other links and lift over

dbSNP: rs112885396; hg19: chr1-175293570; API