1-235433008-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001287801.2(TBCE):​c.723C>T​(p.Phe241Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,521,900 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 137 hom., cov: 31)
Exomes 𝑓: 0.0022 ( 96 hom. )

Consequence

TBCE
NM_001287801.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0190
Variant links:
Genes affected
TBCE (HGNC:11582): (tubulin folding cofactor E) Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
RPS21P1 (HGNC:36401): (ribosomal protein S21 pseudogene 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 1-235433008-C-T is Benign according to our data. Variant chr1-235433008-C-T is described in ClinVar as [Benign]. Clinvar id is 1270754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235433008-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.019 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBCENM_003193.5 linkc.661-1196C>T intron_variant Intron 7 of 16 ENST00000642610.2 NP_003184.1 Q15813-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBCEENST00000642610.2 linkc.661-1196C>T intron_variant Intron 7 of 16 NM_003193.5 ENSP00000494796.1 Q15813-1
ENSG00000285053ENST00000645655.1 linkc.661-1196C>T intron_variant Intron 10 of 19 ENSP00000495202.1 Q15813-1

Frequencies

GnomAD3 genomes
AF:
0.0222
AC:
3371
AN:
151530
Hom.:
136
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0769
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00810
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00321
Gnomad NFE
AF:
0.000529
Gnomad OTH
AF:
0.0187
GnomAD3 exomes
AF:
0.00433
AC:
563
AN:
130050
Hom.:
16
AF XY:
0.00353
AC XY:
252
AN XY:
71396
show subpopulations
Gnomad AFR exome
AF:
0.0698
Gnomad AMR exome
AF:
0.00469
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000959
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000539
Gnomad OTH exome
AF:
0.00287
GnomAD4 exome
AF:
0.00225
AC:
3077
AN:
1370260
Hom.:
96
Cov.:
31
AF XY:
0.00195
AC XY:
1316
AN XY:
676288
show subpopulations
Gnomad4 AFR exome
AF:
0.0753
Gnomad4 AMR exome
AF:
0.00475
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000288
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000253
Gnomad4 OTH exome
AF:
0.00502
GnomAD4 genome
AF:
0.0223
AC:
3388
AN:
151640
Hom.:
137
Cov.:
31
AF XY:
0.0217
AC XY:
1608
AN XY:
74040
show subpopulations
Gnomad4 AFR
AF:
0.0772
Gnomad4 AMR
AF:
0.00809
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000530
Gnomad4 OTH
AF:
0.0186
Alfa
AF:
0.0181
Hom.:
13
Bravo
AF:
0.0249
Asia WGS
AF:
0.00635
AC:
22
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 06, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
3.1
DANN
Benign
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs16832613; hg19: chr1-235596323; API