chr10-133352086-C-G

Variant names:

• chr10-133352086-C-G
• rs781362232
• NM_145202.5:c.208C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145202.5(PRAP1):​c.208C>G​(p.Leu70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,460,864 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: 0.0000096 (0 hom.)
• Consequence: PRAP1 NM_145202.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.22
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051245213).

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.208C>G	p.Leu70Val	missense	Exon 4 of 5	NP_660203.3
	ZNF511-PRAP1	NM_001396060.1		c.880C>G	p.Leu294Val	missense	Exon 8 of 9	NP_001382989.1
	PRAP1	NM_001145201.2		c.208C>G	p.Leu70Val	missense	Exon 4 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.208C>G	p.Leu70Val	missense	Exon 4 of 5	ENSP00000416126.2	Q96NZ9-1
	ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.706C>G	p.Leu236Val	missense	Exon 7 of 8	ENSP00000357542.5	H7BY64
	PRAP1	ENST00000463201.2	TSL:1	c.208C>G	p.Leu70Val	missense	Exon 4 of 5	ENSP00000486265.1	Q96NZ9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000439 AC: 11 AN: 250594 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1460864 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 726736

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

American (AMR) AF: 0.000313 AC: 14 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52452

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

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	0.096
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.2
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.024
Sift	Benign	0.094	T
Sift4G	Benign	0.48	T
Polyphen		0.58	P
Vest4		0.10
MutPred		0.15		Gain of sheet (P = 0.0149)
MVP		0.030
MPC		0.28
ClinPred		0.046	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.036
Mutation Taster		=97/3	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: rs781362232; hg19: chr10-135165590;