chr10-91248516-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032373.5(PCGF5):​c.221C>T​(p.Thr74Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PCGF5
NM_032373.5 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59
Variant links:
Genes affected
PCGF5 (HGNC:28264): (polycomb group ring finger 5) Predicted to enable metal ion binding activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; centrosome; and nucleoplasm. Part of PcG protein complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PCGF5NM_032373.5 linkuse as main transcriptc.221C>T p.Thr74Ile missense_variant 4/10 ENST00000336126.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PCGF5ENST00000336126.6 linkuse as main transcriptc.221C>T p.Thr74Ile missense_variant 4/101 NM_032373.5 P1Q86SE9-1
PCGF5ENST00000614189.4 linkuse as main transcriptc.221C>T p.Thr74Ile missense_variant 4/101 P1Q86SE9-1
PCGF5ENST00000543648.5 linkuse as main transcriptc.221C>T p.Thr74Ile missense_variant 4/102 P1Q86SE9-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152056
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
250742
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135528
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460546
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726612
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152056
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
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:
0.0000113
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsMay 14, 2024The c.221C>T (p.T74I) alteration is located in exon 4 (coding exon 3) of the PCGF5 gene. This alteration results from a C to T substitution at nucleotide position 221, causing the threonine (T) at amino acid position 74 to be replaced by an isoleucine (I). 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
0.97
BayesDel_addAF
Uncertain
0.019
T
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T;T;T
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;.;.
M_CAP
Benign
0.033
D
MetaRNN
Pathogenic
0.80
D;D;D
MetaSVM
Benign
-0.87
T
MutationAssessor
Pathogenic
3.1
M;M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-6.0
.;D;D
REVEL
Uncertain
0.53
Sift
Uncertain
0.0030
.;D;D
Sift4G
Uncertain
0.0090
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.86
MutPred
0.43
Loss of disorder (P = 0.0838);Loss of disorder (P = 0.0838);Loss of disorder (P = 0.0838);
MVP
0.52
MPC
2.2
ClinPred
0.97
D
GERP RS
5.3
Varity_R
0.74
gMVP
0.75

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.

Other links and lift over

dbSNP: rs759182214; hg19: chr10-93008273; API