Variant 7-102396508-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024653.4(PRKRIP1):c.97C>G(p.Leu33Val) variant causes a missense change. The variant allele was found at a frequency of 0.000199 in 1,609,988 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 3 hom. )

Consequence

PRKRIP1
NM_024653.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.65

Variant links:

Genes affected

PRKRIP1 (HGNC:21894): (PRKR interacting protein 1) Predicted to enable double-stranded RNA binding activity; protein kinase binding activity; and protein kinase inhibitor activity. Involved in renal system process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

PRKRIP1 links:

LOC100630923 (HGNC:):

LOC100630923 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009828001).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKRIP1	NM_024653.4 linkuse as main transcript	c.97C>G	p.Leu33Val	missense_variant	1/6	ENST00000397912.3
LOC100630923	NR_038967.1 linkuse as main transcript	n.912-1112C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKRIP1	ENST00000397912.3 linkuse as main transcript	c.97C>G	p.Leu33Val	missense_variant	1/6	1	NM_024653.4	P1	Q9H875-1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000323

AC:

AN:

241184

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

131912

show subpopulations

Gnomad AFR exome

AF:

0.0000660

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.00647

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000561

Gnomad OTH exome

AF:

0.000338

GnomAD4 exome

AF:

0.000195

AC:

285

AN:

1457830

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

131

AN XY:

725276

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.00780

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.000482

GnomAD4 genome

AF:

0.000237

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000788

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000256

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.97C>G (p.L33V) alteration is located in exon 1 (coding exon 1) of the PRKRIP1 gene. This alteration results from a C to G substitution at nucleotide position 97, causing the leucine (L) at amino acid position 33 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.83

M_CAP

Benign

0.013

MetaRNN

Benign

0.0098

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.087

Sift

Uncertain

0.019

D;D

Sift4G

Uncertain

0.029

D;D

Polyphen

0.46

P;P

Vest4

0.45

MVP

0.38

MPC

0.53

ClinPred

0.089

GERP RS

5.2

Varity_R

0.50

gMVP

0.39

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