4-70158463-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_214711.4(PRR27):ā€‹c.211G>Cā€‹(p.Gly71Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

PRR27
NM_214711.4 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.158
Variant links:
Genes affected
PRR27 (HGNC:33193): (proline rich 27) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06927174).
BP6
Variant 4-70158463-G-C is Benign according to our data. Variant chr4-70158463-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2518936.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRR27NM_214711.4 linkc.211G>C p.Gly71Arg missense_variant 3/5 ENST00000344526.10 NP_999876.2 Q6MZM9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRR27ENST00000344526.10 linkc.211G>C p.Gly71Arg missense_variant 3/51 NM_214711.4 ENSP00000343172.5 Q6MZM9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251464
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461842
Hom.:
0
Cov.:
35
AF XY:
0.0000124
AC XY:
9
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMar 31, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
0.40
DANN
Benign
0.34
DEOGEN2
Benign
0.0078
T;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.016
N
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.069
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.75
N;N
PROVEAN
Benign
-0.55
N;N
REVEL
Benign
0.089
Sift
Benign
0.25
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.010
B;B
Vest4
0.11
MutPred
0.47
Gain of glycosylation at Y67 (P = 0.0075);Gain of glycosylation at Y67 (P = 0.0075);
MVP
0.040
MPC
0.038
ClinPred
0.059
T
GERP RS
-2.5
Varity_R
0.049
gMVP
0.15

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.

Other links and lift over

dbSNP: rs1404050578; hg19: chr4-71024180; API