chr7-7639107-C-A

Position:

• chr7-7639107-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002947.5(RPA3):​c.137G>T​(p.Gly46Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPA3 NM_002947.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPA3	NM_002947.5	c.137G>T	p.Gly46Val	missense_variant	6/8	ENST00000223129.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPA3	ENST00000223129.8	c.137G>T	p.Gly46Val	missense_variant	6/8	1	NM_002947.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2023

The c.137G>T (p.G46V) alteration is located in exon 6 (coding exon 2) of the RPA3 gene. This alteration results from a G to T substitution at nucleotide position 137, causing the glycine (G) at amino acid position 46 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	.;.;D;D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Uncertain	-0.056	T
MutationAssessor	Uncertain	2.5	M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.020	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.85
MutPred		0.60		Loss of disorder (P = 0.0204);.;Loss of disorder (P = 0.0204);.;
MVP		0.66
MPC		0.30
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-7678738;