chr10-102140114-A-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_015062.5(PPRC1):​c.1606A>G​(p.Ser536Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,614,220 control chromosomes in the GnomAD database, including 1,296 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.018 ( 135 hom., cov: 32)
Exomes 𝑓: 0.013 ( 1161 hom. )

Consequence

PPRC1
NM_015062.5 missense

Scores

18

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.667

Publications

12 publications found
Variant links:
Genes affected
PPRC1 (HGNC:30025): (PPARG related coactivator 1) The protein encoded by this gene is similar to PPAR-gamma coactivator 1 (PPARGC1/PGC-1), a protein that can activate mitochondrial biogenesis in part through a direct interaction with nuclear respiratory factor 1 (NRF1). This protein has been shown to interact with NRF1. It is thought to be a functional relative of PPAR-gamma coactivator 1 that activates mitochondrial biogenesis through NRF1 in response to proliferative signals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0015044808).
BP6
Variant 10-102140114-A-G is Benign according to our data. Variant chr10-102140114-A-G is described in ClinVar as [Benign]. Clinvar id is 3057089.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPRC1NM_015062.5 linkc.1606A>G p.Ser536Gly missense_variant Exon 5 of 14 ENST00000278070.7 NP_055877.3 Q5VV67-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPRC1ENST00000278070.7 linkc.1606A>G p.Ser536Gly missense_variant Exon 5 of 14 1 NM_015062.5 ENSP00000278070.2 Q5VV67-1
PPRC1ENST00000413464.6 linkc.1606A>G p.Ser536Gly missense_variant Exon 5 of 12 2 ENSP00000399743.2 E7EVG6

Frequencies

GnomAD3 genomes
AF:
0.0180
AC:
2739
AN:
152208
Hom.:
137
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0616
Gnomad ASJ
AF:
0.00548
Gnomad EAS
AF:
0.171
Gnomad SAS
AF:
0.0605
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00193
Gnomad OTH
AF:
0.0211
GnomAD2 exomes
AF:
0.0351
AC:
8824
AN:
251440
AF XY:
0.0331
show subpopulations
Gnomad AFR exome
AF:
0.00843
Gnomad AMR exome
AF:
0.0869
Gnomad ASJ exome
AF:
0.00446
Gnomad EAS exome
AF:
0.191
Gnomad FIN exome
AF:
0.000277
Gnomad NFE exome
AF:
0.00178
Gnomad OTH exome
AF:
0.0215
GnomAD4 exome
AF:
0.0134
AC:
19561
AN:
1461894
Hom.:
1161
Cov.:
33
AF XY:
0.0143
AC XY:
10402
AN XY:
727248
show subpopulations
African (AFR)
AF:
0.00962
AC:
322
AN:
33480
American (AMR)
AF:
0.0867
AC:
3877
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00532
AC:
139
AN:
26136
East Asian (EAS)
AF:
0.195
AC:
7751
AN:
39700
South Asian (SAS)
AF:
0.0566
AC:
4885
AN:
86258
European-Finnish (FIN)
AF:
0.000225
AC:
12
AN:
53420
Middle Eastern (MID)
AF:
0.0276
AC:
159
AN:
5768
European-Non Finnish (NFE)
AF:
0.00132
AC:
1466
AN:
1112012
Other (OTH)
AF:
0.0157
AC:
950
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
1419
2838
4256
5675
7094
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
272
544
816
1088
1360
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0180
AC:
2740
AN:
152326
Hom.:
135
Cov.:
32
AF XY:
0.0207
AC XY:
1543
AN XY:
74490
show subpopulations
African (AFR)
AF:
0.0101
AC:
421
AN:
41580
American (AMR)
AF:
0.0616
AC:
943
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
0.00548
AC:
19
AN:
3470
East Asian (EAS)
AF:
0.171
AC:
885
AN:
5178
South Asian (SAS)
AF:
0.0601
AC:
290
AN:
4826
European-Finnish (FIN)
AF:
0.000282
AC:
3
AN:
10626
Middle Eastern (MID)
AF:
0.0102
AC:
3
AN:
294
European-Non Finnish (NFE)
AF:
0.00193
AC:
131
AN:
68018
Other (OTH)
AF:
0.0213
AC:
45
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
128
257
385
514
642
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
36
72
108
144
180
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0122
Hom.:
269
Bravo
AF:
0.0224
TwinsUK
AF:
0.00162
AC:
6
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.00885
AC:
39
ESP6500EA
AF:
0.00140
AC:
12
ExAC
AF:
0.0324
AC:
3938
Asia WGS
AF:
0.0860
AC:
299
AN:
3478
EpiCase
AF:
0.00354
EpiControl
AF:
0.00296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

PPRC1-related disorder Benign:1
Apr 03, 2019
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
0.060
DANN
Benign
0.83
DEOGEN2
Benign
0.016
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.097
N
LIST_S2
Benign
0.50
T;T
MetaRNN
Benign
0.0015
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.44
.;N
PhyloP100
-0.67
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.69
N;N
REVEL
Benign
0.041
Sift
Benign
0.56
T;T
Sift4G
Benign
0.27
T;T
Polyphen
0.0010
B;B
Vest4
0.067
MPC
0.077
ClinPred
0.0017
T
GERP RS
-6.0
Varity_R
0.035
gMVP
0.12
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs17114388; hg19: chr10-103899871; COSMIC: COSV53384058; COSMIC: COSV53384058; API