rs1452539379

Variant names:

• chr10-133352309-C-A
• rs1452539379
• NM_145202.5:c.325C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145202.5(PRAP1):​c.325C>A​(p.His109Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PRAP1 NM_145202.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.128
• Publications: 1 publications found

Genes affected

PRAP1 (HGNC:23304): (proline rich acidic protein 1) Predicted to enable triglyceride binding activity. Involved in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; deactivation of mitotic spindle assembly checkpoint; and negative regulation of apoptotic process. Predicted to be located in endoplasmic reticulum and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ZNF511-PRAP1 (HGNC:38088): (ZNF511-PRAP1 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ZNF511 (zinc finger protein 511) and PRAP1 (proline-rich acidic protein 1) genes on chromosome 10. The putative readthrough transcript may encode a fusion protein that shares sequence identity with each individual gene product and may be involved in the regulation of gene promoters, particularly those found on transfected plasmids. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0772495).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145202.5. 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
	PRAP1	NM_145202.5	MANE Select	c.325C>A	p.His109Asn	missense	Exon 5 of 5	NP_660203.3
	ZNF511-PRAP1	NM_001396060.1		c.997C>A	p.His333Asn	missense	Exon 9 of 9	NP_001382989.1
	PRAP1	NM_001145201.2		c.298C>A	p.His100Asn	missense	Exon 5 of 5	NP_001138673.1	A6XND8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAP1	ENST00000433452.6	TSL:1 MANE Select	c.325C>A	p.His109Asn	missense	Exon 5 of 5	ENSP00000416126.2	Q96NZ9-1
	ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.823C>A	p.His275Asn	missense	Exon 8 of 8	ENSP00000357542.5	H7BY64
	PRAP1	ENST00000463201.2	TSL:1	c.298C>A	p.His100Asn	missense	Exon 5 of 5	ENSP00000486265.1	Q96NZ9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460876 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726732

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111976

Other (OTH) AF: 0.0000331 AC: 2 AN: 60384

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.5
DANN	Benign	0.67
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.13
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.012
Sift	Benign	0.32	T
Sift4G	Benign	0.32	T
Polyphen		0.26	B
Vest4		0.12
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.014
MPC		0.25
ClinPred		0.083	T
GERP RS		-0.70
Varity_R		0.18
gMVP		0.040
Mutation Taster		=92/8	polymorphism

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: rs1452539379; hg19: chr10-135165813;