rs13118159

chr4-1371339-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
UVSSA	NM_020894.4	c.1289-4025T>C		intron_variant		ENST00000389851.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UVSSA	ENST00000389851.10	c.1289-4025T>C		intron_variant		1	NM_020894.4	P2

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82273 AN: 151260 Hom.: 23371 Cov.: 29

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

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.0955

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.482

Alfa AF: 0.525 Hom.: 19013

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98

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

Other links and lift over

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