Variant 4-70158749-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_214711.4(PRR27):c.497C>G(p.Ala166Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000873 in 1,546,092 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 5 hom. )

Consequence

PRR27
NM_214711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

PRR27 (HGNC:33193): (proline rich 27) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

PRR27 links:

PRR27 (HGNC:):

PRR27 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047601342).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR27	NM_214711.4 linkuse as main transcript	c.497C>G	p.Ala166Gly	missense_variant	3/5	ENST00000344526.10	NP_999876.2	Q6MZM9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR27	ENST00000344526.10 linkuse as main transcript	c.497C>G	p.Ala166Gly	missense_variant	3/5	1	NM_214711.4	ENSP00000343172.5		Q6MZM9

Frequencies

GnomAD3 genomes

AF:

0.0000412

AC:

AN:

145634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000783

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000605

AC:

AN:

247774

Hom.:

AF XY:

0.0000746

AC XY:

AN XY:

134112

show subpopulations

Gnomad AFR exome

AF:

0.0000628

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000660

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000988

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000921

AC:

129

AN:

1400458

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

696178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.0000689

GnomAD4 genome

AF:

0.0000412

AC:

AN:

145634

Hom.:

Cov.:

AF XY:

0.0000421

AC XY:

AN XY:

71214

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000783

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000590

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000840

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

Apr 27, 2022

The c.497C>G (p.A166G) alteration is located in exon 3 (coding exon 3) of the PRR27 gene. This alteration results from a C to G substitution at nucleotide position 497, causing the alanine (A) at amino acid position 166 to be replaced by a glycine (G). 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

0.10

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.91

DANN

Benign

0.58

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.027

M_CAP

Benign

0.0023

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.028

Sift

Benign

0.11

T;T

Sift4G

Benign

0.092

T;T

Polyphen

0.022

B;B

Vest4

0.092

MVP

0.014

MPC

0.030

ClinPred

0.017

GERP RS

-4.0

Varity_R

0.040

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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