Genetic Variant PRND:p.Pro56Leu (chr20-4724718-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012409.4(PRND):c.167C>T(p.Pro56Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00934 in 1,614,168 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0073 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 95 hom. )

Consequence

PRND
NM_012409.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

PRND (HGNC:15748): (prion like protein doppel) This gene is found on chromosome 20, approximately 20 kbp downstream of the gene encoding cellular prion protein, to which it is biochemically and structurally similar. The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that is found predominantly in testis. Mutations in this gene may lead to neurological disorders. [provided by RefSeq, Jul 2008]

PRND links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010197222).

BP6

Variant 20-4724718-C-T is Benign according to our data. Variant chr20-4724718-C-T is described in ClinVar as [Benign]. Clinvar id is 773779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRND	NM_012409.4 link	c.167C>T	p.Pro56Leu	missense_variant	Exon 2 of 2	ENST00000305817.3	NP_036541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRND	ENST00000305817.3 link	c.167C>T	p.Pro56Leu	missense_variant	Exon 2 of 2	1	NM_012409.4	ENSP00000306900.2		Q9UKY0

Frequencies

GnomAD3 genomes

AF:

0.00731

AC:

1113

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00806

AC:

2026

AN:

251296

Hom.:

AF XY:

0.00813

AC XY:

1105

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00587

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00946

GnomAD4 exome

AF:

0.00955

AC:

13964

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

6774

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00555

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00402

Gnomad4 FIN exome

AF:

0.0128

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.00747

GnomAD4 genome

AF:

0.00730

AC:

1112

AN:

152294

Hom.:

Cov.:

AF XY:

0.00723

AC XY:

538

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0119

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00898

Hom.:

Bravo

AF:

0.00684

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0127

AC:

109

ExAC

AF:

0.00887

AC:

1077

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00965

EpiControl

AF:

0.00889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.069

Sift

Benign

0.032

Sift4G

Benign

0.071

Polyphen

0.97

Vest4

0.20

MVP

0.65

MPC

0.45

ClinPred

0.017

GERP RS

4.4

Varity_R

0.10

gMVP

0.50

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

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