2-74505958-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_032673.3(PCGF1):​c.524G>A​(p.Arg175Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PCGF1
NM_032673.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60
Variant links:
Genes affected
PCGF1 (HGNC:17615): (polycomb group ring finger 1) PCGF1 is a mammalian homolog of the Drosophila polycomb group genes, which act as transcriptional repressors to regulate anterior-posterior patterning in early embryonic development (Nunes et al., 2001 [PubMed 11287196]). See also PCGF2 (MIM 600346).[supplied by OMIM, Aug 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.28184354).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCGF1NM_032673.3 linkc.524G>A p.Arg175Gln missense_variant Exon 5 of 9 ENST00000233630.11 NP_116062.2 Q9BSM1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCGF1ENST00000233630.11 linkc.524G>A p.Arg175Gln missense_variant Exon 5 of 9 1 NM_032673.3 ENSP00000233630.6 Q9BSM1-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461740
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727178
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.524G>A (p.R175Q) alteration is located in exon 5 (coding exon 5) of the PCGF1 gene. This alteration results from a G to A substitution at nucleotide position 524, causing the arginine (R) at amino acid position 175 to be replaced by a glutamine (Q). 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
0.20
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
24
DANN
Benign
0.66
DEOGEN2
Benign
0.058
T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.40
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.99
N
REVEL
Benign
0.11
Sift
Benign
0.58
T
Sift4G
Benign
0.30
T
Polyphen
0.44
B
Vest4
0.43
MutPred
0.45
Gain of ubiquitination at K180 (P = 0.0453);
MVP
0.51
MPC
1.0
ClinPred
0.50
D
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.23
gMVP
0.43

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: rs201383050; hg19: chr2-74733085; COSMIC: COSV52042980; COSMIC: COSV52042980; API