Variant 2-27137698-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000335524.7(PRR30):c.632T>C(p.Leu211Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,500 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRR30
ENST00000335524.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

Variant links:

Genes affected

PRR30 (HGNC:28677): (proline rich 30)

PRR30 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR30	NM_178553.4 linkuse as main transcript	c.632T>C	p.Leu211Pro	missense_variant	3/3	ENST00000335524.7	NP_848648.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR30	ENST00000335524.7 linkuse as main transcript	c.632T>C	p.Leu211Pro	missense_variant	3/3	1	NM_178553.4	ENSP00000335017	P1
PRR30	ENST00000432962.2 linkuse as main transcript	c.138T>C	p.Pro46=	synonymous_variant	4/4	3		ENSP00000393468

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

247484

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461272

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

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

Jul 11, 2023

The c.632T>C (p.L211P) alteration is located in exon 3 (coding exon 1) of the PRR30 gene. This alteration results from a T to C substitution at nucleotide position 632, causing the leucine (L) at amino acid position 211 to be replaced by a proline (P). 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

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.44

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.87

MutPred

0.64

Gain of loop (P = 0.0045);

MVP

0.53

MPC

0.92

ClinPred

0.95

GERP RS

4.7

Varity_R

0.89

gMVP

0.70

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