Variant 10-91271641-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_032373.5(PCGF5):c.667C>T(p.Arg223Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,390 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PCGF5
NM_032373.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

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]

PCGF5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCGF5	NM_032373.5 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	9/10	ENST00000336126.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCGF5	ENST00000336126.6 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	9/10	1	NM_032373.5	P1	Q86SE9-1
PCGF5	ENST00000614189.4 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	9/10	1		P1	Q86SE9-1
PCGF5	ENST00000543648.5 linkuse as main transcript	c.667C>T	p.Arg223Trp	missense_variant	9/10	2		P1	Q86SE9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251004

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461390

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000412

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

Mar 30, 2024

The c.667C>T (p.R223W) alteration is located in exon 9 (coding exon 8) of the PCGF5 gene. This alteration results from a C to T substitution at nucleotide position 667, causing the arginine (R) at amino acid position 223 to be replaced by a tryptophan (W). 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

0.25

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.93

D;.;.

M_CAP

Benign

0.0095

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.2

.;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0030

.;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

0.98

D;D;D

Vest4

0.70

MutPred

0.57

Loss of methylation at R223 (P = 0.014);Loss of methylation at R223 (P = 0.014);Loss of methylation at R223 (P = 0.014);

MVP

0.38

MPC

1.1

ClinPred

0.16

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.091

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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