chr17-5426255-A-G

Variant names:

• chr17-5426255-A-G
• rs77813450
• NM_001033002.4:c.445A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001033002.4(RPAIN):​c.445A>G​(p.Ser149Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,614,110 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (70 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (64 hom.)
• Consequence: RPAIN NM_001033002.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.812
• Publications: 8 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019278228).
• BP6: Variant 17-5426255-A-G is Benign according to our data. Variant chr17-5426255-A-G is described in ClinVar as Benign. ClinVar VariationId is 780394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

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.445A>G	p.Ser149Gly	missense	Exon 5 of 7	NP_001028174.2	Q86UA6-1
	RPAIN	NM_001160243.2		c.445A>G	p.Ser149Gly	missense	Exon 5 of 6	NP_001153715.1	Q86UA6-8
	RPAIN	NM_001160244.2		c.445A>G	p.Ser149Gly	missense	Exon 5 of 6	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.445A>G	p.Ser149Gly	missense	Exon 5 of 7	ENSP00000370606.3	Q86UA6-1
	RPAIN	ENST00000381208.9	TSL:1	c.445A>G	p.Ser149Gly	missense	Exon 5 of 6	ENSP00000370605.5	Q86UA6-2
	RPAIN	ENST00000536255.6	TSL:1	c.313+3426A>G		intron	N/A	ENSP00000439939.2	Q86UA6-6

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2432 AN: 152140 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00780

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00405 AC: 1019 AN: 251488 AF XY: 0.00291

Gnomad AFR exome AF: 0.0547

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00173 AC: 2524 AN: 1461852 Hom.: 64 Cov.: 31 AF XY: 0.00151 AC XY: 1096 AN XY: 727228

African (AFR) AF: 0.0595 AC: 1993 AN: 33474

American (AMR) AF: 0.00297 AC: 133 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.0000872 AC: 97 AN: 1111980

Other (OTH) AF: 0.00407 AC: 246 AN: 60392

GnomAD4 genome AF: 0.0160 AC: 2440 AN: 152258 Hom.: 70 Cov.: 32 AF XY: 0.0154 AC XY: 1147 AN XY: 74442

African (AFR) AF: 0.0544 AC: 2261 AN: 41532

American (AMR) AF: 0.00779 AC: 119 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68018

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00686 Hom.: 54

Bravo AF: 0.0194

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0499 AC: 220

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00495 AC: 601

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.81
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.080	N
PhyloP100		-0.81
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.044
Sift	Benign	0.38	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.13
MVP		0.061
MPC		0.093
ClinPred		0.0023	T
GERP RS		-7.5
Varity_R		0.037
gMVP		0.21
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs77813450; hg19: chr17-5329575;