chr4-1371339-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B.

Score: -12 - Benign
-12
-12 -7 -6 -1 0 5 6 9 10 12
BP4_StrongBA1

The NM_020894.4(UVSSA):​c.1289-4025T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,378 control chromosomes in the GnomAD database, including 23,398 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 0.54 ( 23398 hom., cov: 29)

Consequence

UVSSA
NM_020894.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.20

Publications

21 publications found
Variant links:
Genes affected
UVSSA (HGNC:29304): (UV stimulated scaffold protein A) The protein encoded by this gene appears to be involved in ubiquitination and dephosphorylation of RNA polymerase II subunits that stall after UV irradiation. The encoded protein interacts with several members of the nucleotide excision repair complex, and is thought to be involved in the transcription-coupled nucleotide excision repair (TC-NER) pathway to help remove lesions in the DNA that block transcription. Defects in this gene can cause UV-sensitive syndrome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
UVSSA Gene-Disease associations (from GenCC):
  • UV-sensitive syndrome 3
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • UV-sensitive syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.04).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UVSSANM_020894.4 linkc.1289-4025T>C intron_variant Intron 8 of 13 ENST00000389851.10 NP_065945.2 Q2YD98-1Q69YU2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UVSSAENST00000389851.10 linkc.1289-4025T>C intron_variant Intron 8 of 13 1 NM_020894.4 ENSP00000374501.4 Q2YD98-1

Frequencies

GnomAD3 genomes
AF:
0.544
AC:
82273
AN:
151260
Hom.:
23371
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.654
Gnomad AMI
AF:
0.610
Gnomad AMR
AF:
0.478
Gnomad ASJ
AF:
0.426
Gnomad EAS
AF:
0.0963
Gnomad SAS
AF:
0.313
Gnomad FIN
AF:
0.540
Gnomad MID
AF:
0.424
Gnomad NFE
AF:
0.550
Gnomad OTH
AF:
0.482
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.544
AC:
82350
AN:
151378
Hom.:
23398
Cov.:
29
AF XY:
0.535
AC XY:
39520
AN XY:
73924
show subpopulations
African (AFR)
AF:
0.654
AC:
26954
AN:
41190
American (AMR)
AF:
0.478
AC:
7261
AN:
15192
Ashkenazi Jewish (ASJ)
AF:
0.426
AC:
1479
AN:
3470
East Asian (EAS)
AF:
0.0955
AC:
491
AN:
5140
South Asian (SAS)
AF:
0.313
AC:
1499
AN:
4782
European-Finnish (FIN)
AF:
0.540
AC:
5631
AN:
10422
Middle Eastern (MID)
AF:
0.421
AC:
123
AN:
292
European-Non Finnish (NFE)
AF:
0.550
AC:
37346
AN:
67882
Other (OTH)
AF:
0.482
AC:
1012
AN:
2100
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1790
3581
5371
7162
8952
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
690
1380
2070
2760
3450
<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:
0.536
Hom.:
59067
Bravo
AF:
0.544
Asia WGS
AF:
0.281
AC:
980
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.45
DANN
Benign
0.30
PhyloP100
-2.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
0.98
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs13118159; hg19: chr4-1365127; COSMIC: COSV66230137; COSMIC: COSV66230137; API