17-5428110-G-A

Variant names:

• chr17-5428110-G-A
• rs763342597
• NM_001033002.4:c.529G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001033002.4(RPAIN):​c.529G>A​(p.Glu177Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E177Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPAIN NM_001033002.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.02
• Publications: 0 publications found

Genes affected

RPAIN (HGNC:28641): (RPA interacting protein) Predicted to enable metal ion binding activity. Acts upstream of or within several processes, including DNA metabolic process; protein import into nucleus; and response to UV. Located in PML body; cytoplasm; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000263272 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033002.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPAIN	NM_001033002.4	MANE Select	c.529G>A	p.Glu177Lys	missense	Exon 6 of 7	NP_001028174.2	Q86UA6-1
	RPAIN	NM_001160243.2		c.529G>A	p.Glu177Lys	missense	Exon 6 of 6	NP_001153715.1	Q86UA6-8
	RPAIN	NM_001160244.2		c.489+1811G>A		intron	N/A	NP_001153716.1	Q86UA6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPAIN	ENST00000381209.8	TSL:1 MANE Select	c.529G>A	p.Glu177Lys	missense	Exon 6 of 7	ENSP00000370606.3	Q86UA6-1
	RPAIN	ENST00000381208.9	TSL:1	c.489+1811G>A		intron	N/A	ENSP00000370605.5	Q86UA6-2
	RPAIN	ENST00000536255.6	TSL:1	c.314-4432G>A		intron	N/A	ENSP00000439939.2	Q86UA6-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.0
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.55		Gain of ubiquitination at E177 (P = 0.0185)
MVP		0.79
MPC		0.54
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.44
gMVP		0.60

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: rs763342597; hg19: chr17-5331430;