chr5-700878-A-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The XM_024454346.1(TPPP):​c.-238T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 151,740 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0062 ( 3 hom., cov: 35)

Consequence

TPPP
XM_024454346.1 upstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

Publications

2 publications found
Variant links:
Genes affected
TPPP (HGNC:24164): (tubulin polymerization promoting protein) Enables several functions, including GTPase activity; magnesium ion binding activity; and protein homodimerization activity. Involved in several processes, including microtubule cytoskeleton organization; negative regulation of tubulin deacetylation; and positive regulation of protein polymerization. Located in several cellular components, including mitochondrion; mitotic spindle; and perinuclear region of cytoplasm. Colocalizes with microtubule and microtubule bundle. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.01).
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TPPPXM_024454346.1 linkc.-238T>C upstream_gene_variant XP_024310114.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt

Frequencies

GnomAD3 genomes
AF:
0.00617
AC:
936
AN:
151624
Hom.:
3
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.00143
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00362
Gnomad ASJ
AF:
0.00520
Gnomad EAS
AF:
0.00213
Gnomad SAS
AF:
0.000625
Gnomad FIN
AF:
0.0200
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.00840
Gnomad OTH
AF:
0.00335
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00616
AC:
935
AN:
151740
Hom.:
3
Cov.:
35
AF XY:
0.00628
AC XY:
466
AN XY:
74190
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00142
AC:
59
AN:
41406
American (AMR)
AF:
0.00361
AC:
55
AN:
15228
Ashkenazi Jewish (ASJ)
AF:
0.00520
AC:
18
AN:
3460
East Asian (EAS)
AF:
0.00213
AC:
11
AN:
5164
South Asian (SAS)
AF:
0.000417
AC:
2
AN:
4794
European-Finnish (FIN)
AF:
0.0200
AC:
211
AN:
10546
Middle Eastern (MID)
AF:
0.00342
AC:
1
AN:
292
European-Non Finnish (NFE)
AF:
0.00839
AC:
569
AN:
67830
Other (OTH)
AF:
0.00427
AC:
9
AN:
2110
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.389
Heterozygous variant carriers
0
37
73
110
146
183
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0110
Hom.:
1
Asia WGS
AF:
0.00867
AC:
30
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
1.9
DANN
Benign
0.25
PhyloP100
-1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs321096; hg19: chr5-700993; API