chr17-5426079-C-T

Variant names:

• chr17-5426079-C-T
• rs532203608
• NM_001033002.4:c.422C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033002.4(RPAIN):​c.422C>T​(p.Thr141Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPAIN NM_001033002.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13175699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPAIN	NM_001033002.4	c.422C>T	p.Thr141Ile	missense_variant	Exon 4 of 7	ENST00000381209.8	NP_001028174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPAIN	ENST00000381209.8	c.422C>T	p.Thr141Ile	missense_variant	Exon 4 of 7	1	NM_001033002.4	ENSP00000370606.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249756 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134986

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456010 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724616

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0098	T;.;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.58	T;T;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.010	B;.;.;.
Vest4		0.20
MutPred		0.38		Gain of ubiquitination at K142 (P = 0.0441);Gain of ubiquitination at K142 (P = 0.0441);Gain of ubiquitination at K142 (P = 0.0441);Gain of ubiquitination at K142 (P = 0.0441);
MVP		0.45
MPC		0.12
ClinPred		0.051	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.023
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs532203608; hg19: chr17-5329399;