rs3735460

chr7-7640254-G-A

Variant summary

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

The NM_002947.5(RPA3):c.99+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,519,680 control chromosomes in the GnomAD database, including 7,685 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 0.081 (698 hom., cov: 32)
  • Exomes 𝑓: 0.096 (6987 hom.)
• Consequence: RPA3 NM_002947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

Genes affected

RPA3 (HGNC:10291): (replication protein A3) Enables damaged DNA binding activity and single-stranded DNA binding activity. Involved in DNA repair and DNA replication. Part of DNA replication factor A complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPA3	NM_002947.5	c.99+66C>T		intron_variant		ENST00000223129.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPA3	ENST00000223129.8	c.99+66C>T		intron_variant		1	NM_002947.5	P1

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12352 AN: 152072 Hom.: 692 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.0929

Gnomad SAS AF: 0.0999

Gnomad FIN AF: 0.0971

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.0891

GnomAD4 exome AF: 0.0957 AC: 130901 AN: 1367490 Hom.: 6987 Cov.: 21 AF XY: 0.0951 AC XY: 65174 AN XY: 685362

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.0859

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.0993

Gnomad4 FIN exome AF: 0.0871

Gnomad4 NFE exome AF: 0.0929

Gnomad4 OTH exome AF: 0.0948

GnomAD4 genome AF: 0.0813 AC: 12373 AN: 152190 Hom.: 698 Cov.: 32 AF XY: 0.0831 AC XY: 6183 AN XY: 74394

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.0929

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0971

Gnomad4 NFE AF: 0.0931

Gnomad4 OTH AF: 0.0891

Alfa AF: 0.0928 Hom.: 766

Bravo AF: 0.0860

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	4.9
Dann	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3735460; hg19: chr7-7679885;