NM_020719.3:c.5498-1531T>C

Variant names:

• chr19-49618821-T-C
• rs11880923
• NM_020719.3:c.5498-1531T>C

Variant summary

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

The NM_020719.3(PRR12):​c.5498-1531T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,446 control chromosomes in the GnomAD database, including 15,720 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 0.43 (15720 hom., cov: 28)
• Consequence: PRR12 NM_020719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 11 publications found

Genes affected

PRR12 (HGNC:29217): (proline rich 12) This gene encodes a proline-rich protein that contains two A-T hook DNA binding domains. A chromosomal translocation and gene fusion between this gene and zinc finger, MIZ-type containing 1 (Gene ID: 57178) may underlie intellectual disability and neuropsychiatric problems in a human patient. Enriched expression of this gene in embryonic mouse brain suggests that this gene may play a role in nervous system development. [provided by RefSeq, Jul 2016]

PRR12 Gene-Disease associations (from GenCC):

• neuroocular syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR12	NM_020719.3	MANE Select	c.5498-1531T>C		intron	N/A	NP_065770.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR12	ENST00000418929.7	TSL:5 MANE Select	c.5498-1531T>C		intron	N/A	ENSP00000394510.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64710 AN: 151328 Hom.: 15683 Cov.: 28

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.428 AC: 64800 AN: 151446 Hom.: 15720 Cov.: 28 AF XY: 0.420 AC XY: 31085 AN XY: 73972

African (AFR) AF: 0.671 AC: 27615 AN: 41164

American (AMR) AF: 0.382 AC: 5810 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1092 AN: 3466

East Asian (EAS) AF: 0.206 AC: 1058 AN: 5134

South Asian (SAS) AF: 0.502 AC: 2399 AN: 4780

European-Finnish (FIN) AF: 0.227 AC: 2383 AN: 10504

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23040 AN: 67882

Other (OTH) AF: 0.421 AC: 886 AN: 2104

Alfa AF: 0.360 Hom.: 29130

Bravo AF: 0.447

Asia WGS AF: 0.401 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.40
PhyloP100		-1.8
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: rs11880923; hg19: chr19-50122078;