10-133347446-C-T

Variant names:

• chr10-133347446-C-T
• rs4838721
• NM_145202.5:c.8+21C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145202.5(PRAP1):​c.8+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,606,498 control chromosomes in the GnomAD database, including 519,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (40761 hom., cov: 34)
  • Exomes 𝑓: 0.81 (479024 hom.)
• Consequence: PRAP1 NM_145202.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 16 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]

ENSG00000226699 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAP1	NM_145202.5	c.8+21C>T		intron_variant	Intron 1 of 4	ENST00000433452.6	NP_660203.3
ZNF511-PRAP1	NM_001396060.1	c.681-2649C>T		intron_variant	Intron 5 of 8		NP_001382989.1
PRAP1	NM_001145201.2	c.8+21C>T		intron_variant	Intron 1 of 4		NP_001138673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAP1	ENST00000433452.6	c.8+21C>T		intron_variant	Intron 1 of 4	1	NM_145202.5	ENSP00000416126.2
ZNF511-PRAP1	ENST00000368554.8	c.507-2649C>T		intron_variant	Intron 4 of 7	2		ENSP00000357542.5
PRAP1	ENST00000463201.2	c.8+21C>T		intron_variant	Intron 1 of 4	1		ENSP00000486265.1
ENSG00000226699	ENST00000452591.1	n.141-1649G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108771 AN: 152046 Hom.: 40744 Cov.: 34

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.729

GnomAD2 exomes AF: 0.795 AC: 193048 AN: 242732 AF XY: 0.803

Gnomad AFR exome AF: 0.465

Gnomad AMR exome AF: 0.745

Gnomad ASJ exome AF: 0.823

Gnomad EAS exome AF: 0.939

Gnomad FIN exome AF: 0.851

Gnomad NFE exome AF: 0.816

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.809 AC: 1176897 AN: 1454334 Hom.: 479024 Cov.: 38 AF XY: 0.811 AC XY: 586256 AN XY: 723282

African (AFR) AF: 0.467 AC: 15533 AN: 33242

American (AMR) AF: 0.742 AC: 32715 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 21221 AN: 25554

East Asian (EAS) AF: 0.908 AC: 35744 AN: 39386

South Asian (SAS) AF: 0.819 AC: 69901 AN: 85316

European-Finnish (FIN) AF: 0.850 AC: 45134 AN: 53122

Middle Eastern (MID) AF: 0.750 AC: 4295 AN: 5730

European-Non Finnish (NFE) AF: 0.817 AC: 904858 AN: 1107842

Other (OTH) AF: 0.791 AC: 47496 AN: 60030

GnomAD4 genome AF: 0.715 AC: 108818 AN: 152164 Hom.: 40761 Cov.: 34 AF XY: 0.720 AC XY: 53571 AN XY: 74404

African (AFR) AF: 0.473 AC: 19625 AN: 41512

American (AMR) AF: 0.732 AC: 11191 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2847 AN: 3470

East Asian (EAS) AF: 0.928 AC: 4783 AN: 5156

South Asian (SAS) AF: 0.810 AC: 3912 AN: 4828

European-Finnish (FIN) AF: 0.847 AC: 8983 AN: 10606

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55162 AN: 67988

Other (OTH) AF: 0.732 AC: 1547 AN: 2112

Alfa AF: 0.751 Hom.: 8938

Bravo AF: 0.696

Asia WGS AF: 0.833 AC: 2899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.2
DANN	Benign	0.82
PhyloP100		0.28
PromoterAI		-0.028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4838721; hg19: chr10-135160950; COSMIC: COSV63918572; COSMIC: COSV63918572;