rs1555741826

Positions:

• chr19-49601645-GCTGC-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_020719.3(PRR12):​c.4502_4505del​(p.Leu1501ArgfsTer146) 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: 31)
• Consequence: PRR12 NM_020719.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 2.18

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 12 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 19-49601645-GCTGC-G is Pathogenic according to our data. Variant chr19-49601645-GCTGC-G is described in ClinVar as [Pathogenic]. Clinvar id is 446255.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-49601645-GCTGC-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR12	NM_020719.3	c.4502_4505del	p.Leu1501ArgfsTer146	frameshift_variant	6/14	ENST00000418929.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR12	ENST00000418929.7	c.4502_4505del	p.Leu1501ArgfsTer146	frameshift_variant	6/14	5	NM_020719.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Neuroocular syndrome 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 30, 2024

- -

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 8-year-old male with delayed motor milestones, delayed speech, intellectual disability, hypotonia, unilateral sensorineural hearing loss, dysmorphic features (downslanting palpebral fissures, ptosis, mid-face hypoplasia, low set ears), short stature, eye anomalies (esotropia, stellate iris, distichiasis), vision loss, and skeletal abnormalities (scapular winging). -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs1555741826; hg19: chr19-50104902;