10-133352086-C-A

Variant names:

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

Variant summary

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

The NM_145202.5(PRAP1):​c.208C>A​(p.Leu70Ile) 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 1,460,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000021 (0 hom.)
• Consequence: PRAP1 NM_145202.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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

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=0.09546322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAP1	NM_145202.5	c.208C>A	p.Leu70Ile	missense_variant	Exon 4 of 5	ENST00000433452.6	NP_660203.3
ZNF511-PRAP1	NM_001396060.1	c.880C>A	p.Leu294Ile	missense_variant	Exon 8 of 9		NP_001382989.1
PRAP1	NM_001145201.2	c.208C>A	p.Leu70Ile	missense_variant	Exon 4 of 5		NP_001138673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAP1	ENST00000433452.6	c.208C>A	p.Leu70Ile	missense_variant	Exon 4 of 5	1	NM_145202.5	ENSP00000416126.2
ZNF511-PRAP1	ENST00000368554.8	c.706C>A	p.Leu236Ile	missense_variant	Exon 7 of 8	2		ENSP00000357542.5
PRAP1	ENST00000463201.2	c.208C>A	p.Leu70Ile	missense_variant	Exon 4 of 5	1		ENSP00000486265.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460864 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726736

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

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	0.091
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PROVEAN	Benign	-0.97	N;.
REVEL	Benign	0.065
Sift	Benign	0.14	T;.
Sift4G	Benign	0.28	T;T
Polyphen		0.89	P;.
Vest4		0.15
MutPred		0.15		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.030
MPC		0.36
ClinPred		0.41	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.025

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-135165590;