10-133322568-T-C

Variant names:

• chr10-133322568-T-C
• rs2105341
• ENST00000368554.8:c.506+10727T>C

Variant summary

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

The NM_001396060.1(ZNF511-PRAP1):​c.680+10727T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 150,730 control chromosomes in the GnomAD database, including 2,773 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 0.18 (2773 hom., cov: 31)
• Consequence: ZNF511-PRAP1 NM_001396060.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 3 publications found

Genes affected

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396060.1. 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
	ZNF511-PRAP1	NM_001396060.1		c.680+10727T>C		intron	N/A	NP_001382989.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF511-PRAP1	ENST00000368554.8	TSL:2	c.506+10727T>C		intron	N/A	ENSP00000357542.5	H7BY64

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27104 AN: 150618 Hom.: 2757 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0680

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.180 AC: 27151 AN: 150730 Hom.: 2773 Cov.: 31 AF XY: 0.177 AC XY: 13052 AN XY: 73720

African (AFR) AF: 0.264 AC: 10910 AN: 41288

American (AMR) AF: 0.215 AC: 3276 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 504 AN: 3450

East Asian (EAS) AF: 0.0677 AC: 347 AN: 5124

South Asian (SAS) AF: 0.134 AC: 643 AN: 4786

European-Finnish (FIN) AF: 0.120 AC: 1250 AN: 10442

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9517 AN: 67130

Other (OTH) AF: 0.188 AC: 390 AN: 2080

Alfa AF: 0.164 Hom.: 292

Bravo AF: 0.190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.5
DANN	Benign	0.16
PhyloP100		0.15
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: rs2105341; hg19: chr10-135136072;