Genetic Variant UVSSA:c.1289-4025T>C (chr4-1371339-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

-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

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

UVSSA links:

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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
UVSSA	NM_020894.4 link	c.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
UVSSA	ENST00000389851.10 link	c.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.:

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.:

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

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

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

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over