rs1555740394

Positions:

• chr19-49595234-C-CCCCACCA

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_020719.3(PRR12):​c.903_909dup​(p.Pro304ThrfsTer46) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRR12 NM_020719.3 frameshift
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:2
• Conservation: PhyloP100: 0.0250

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]

ACMG classification

Verdict is Pathogenic. Variant got 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-49595234-C-CCCCACCA is Pathogenic according to our data. Variant chr19-49595234-C-CCCCACCA is described in ClinVar as [Pathogenic]. Clinvar id is 446256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR12	NM_020719.3	c.903_909dup	p.Pro304ThrfsTer46	frameshift_variant	4/14	ENST00000418929.7	NP_065770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR12	ENST00000418929.7	c.903_909dup	p.Pro304ThrfsTer46	frameshift_variant	4/14	5	NM_020719.3	ENSP00000394510	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neuroocular syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Daryl Scott Lab, Baylor College of Medicine

Nov 10, 2023

- -

Autism;C0240063:Iris coloboma;C0454644:Delayed speech and language development;C1854301:Motor delay;C4025846:Abnormality of vision Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Nov 15, 2017

This variant was seen once in our laboratory de novo in a 6.6-year-old male with bilateral inferior iris coloboma, myopia, exotropia, vision loss, delayed motor milestones, delayed speech, attention deficit hyperactivity disorder, anxiety, possible hypertonia, brisk reflexes, microcephaly, dysmorphic features, patent foramen ovale, central obstructive sleep apnea, tibial torsion, pes planus, joint laxity, easy bruising, eczema and a history of umbilical hernia and ankyloglossia. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555740394; hg19: chr19-50098491;