19-49591652-T-G

Position:

• chr19-49591652-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_Moderate BP6

The NM_020719.3(PRR12):​c.-3T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000037 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRR12 NM_020719.3 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.13

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 Likely_benign. Variant got -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 19-49591652-T-G is Benign according to our data. Variant chr19-49591652-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3038571.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR12	NM_020719.3	c.-3T>G		5_prime_UTR_variant	1/14	ENST00000418929.7	NP_065770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR12	ENST00000418929	c.-3T>G		5_prime_UTR_variant	1/14	5	NM_020719.3	ENSP00000394510.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4 AN: 107196 Hom.: 0 Cov.: 21 FAILED QC

Gnomad AFR AF: 0.0000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000322

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000346

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000262 AC: 246 AN: 939594 Hom.: 0 Cov.: 26 AF XY: 0.000232 AC XY: 108 AN XY: 465248

Gnomad4 AFR exome AF: 0.000292

Gnomad4 AMR exome AF: 0.000688

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.00183

Gnomad4 SAS exome AF: 0.0000645

Gnomad4 FIN exome AF: 0.00153

Gnomad4 NFE exome AF: 0.000171

Gnomad4 OTH exome AF: 0.000555

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000373 AC: 4 AN: 107224 Hom.: 0 Cov.: 21 AF XY: 0.0000620 AC XY: 3 AN XY: 48386

Gnomad4 AFR AF: 0.0000362

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000322

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000346

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PRR12-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: chr19-50094909;