chr4-1371339-T-C

Variant names:

• chr4-1371339-T-C
• rs13118159
• NM_020894.4:c.1289-4025T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

ACMG classification

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	c.1289-4025T>C		intron_variant	Intron 8 of 13	ENST00000389851.10	NP_065945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UVSSA	ENST00000389851.10	c.1289-4025T>C		intron_variant	Intron 8 of 13	1	NM_020894.4	ENSP00000374501.4

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

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

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

Other links and lift over

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