Variant 19-49594489-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020719.3(PRR12):c.235G>A(p.Ala79Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,612,270 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 6 hom. )

Consequence

PRR12
NM_020719.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.56

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009969711).

BP6

Variant 19-49594489-G-A is Benign according to our data. Variant chr19-49594489-G-A is described in ClinVar as [Benign]. Clinvar id is 774961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00153 (232/151968) while in subpopulation NFE AF= 0.00286 (194/67938). AF 95% confidence interval is 0.00253. There are 0 homozygotes in gnomad4. There are 93 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 232 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR12	NM_020719.3 linkuse as main transcript	c.235G>A	p.Ala79Thr	missense_variant	3/14	ENST00000418929.7	NP_065770.1	Q9ULL5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR12	ENST00000418929.7 linkuse as main transcript	c.235G>A	p.Ala79Thr	missense_variant	3/14	5	NM_020719.3	ENSP00000394510.1		Q9ULL5-3

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

232

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000412

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000662

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00286

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00150

AC:

372

AN:

247190

Hom.:

AF XY:

0.00135

AC XY:

182

AN XY:

134378

show subpopulations

Gnomad AFR exome

AF:

0.000326

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000420

Gnomad NFE exome

AF:

0.00303

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00234

AC:

3417

AN:

1460302

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1640

AN XY:

726386

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000270

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000792

Gnomad4 NFE exome

AF:

0.00295

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00153

AC:

232

AN:

151968

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000662

Gnomad4 NFE

AF:

0.00286

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00201

Hom.:

Bravo

AF:

0.00135

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000794

AC:

ESP6500EA

AF:

0.00257

AC:

ExAC

AF:

0.00185

AC:

224

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PRR12-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 09, 2023

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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.94

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.73

M_CAP

Benign

0.0067

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.5

REVEL

Benign

0.11

Sift

Benign

0.037

Sift4G

Uncertain

0.034

Polyphen

1.0

Vest4

0.25

MVP

0.27

MPC

0.41

ClinPred

0.047

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over