Genetic Variant PCGF5:p.Asp124Tyr (chr10-91251336-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032373.5(PCGF5):c.370G>T(p.Asp124Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000323 in 1,610,668 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

PCGF5
NM_032373.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14293763).

BS2

High AC in GnomAdExome4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCGF5	NM_032373.5 link	c.370G>T	p.Asp124Tyr	missense_variant	Exon 6 of 10	ENST00000336126.6	NP_115749.2	Q86SE9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCGF5	ENST00000336126.6 link	c.370G>T	p.Asp124Tyr	missense_variant	Exon 6 of 10	1	NM_032373.5	ENSP00000337500.5	Q86SE9-1
PCGF5	ENST00000614189.4 link	c.370G>T	p.Asp124Tyr	missense_variant	Exon 6 of 10	1		ENSP00000479492.1	Q86SE9-1
PCGF5	ENST00000543648.5 link	c.370G>T	p.Asp124Tyr	missense_variant	Exon 6 of 10	2		ENSP00000445704.1	Q86SE9-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

250066

Hom.:

AF XY:

0.0000814

AC XY:

AN XY:

135200

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:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000343

AC:

AN:

1458754

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

725822

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:

0.000546

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151914

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.370G>T (p.D124Y) alteration is located in exon 6 (coding exon 5) of the PCGF5 gene. This alteration results from a G to T substitution at nucleotide position 370, causing the aspartic acid (D) at amino acid position 124 to be replaced by a tyrosine (Y). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

T;T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.91

D;.;.

M_CAP

Benign

0.0055

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.1

.;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.018

.;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.91

P;P;P

Vest4

0.46

MutPred

0.31

Gain of phosphorylation at D124 (P = 0.0033);Gain of phosphorylation at D124 (P = 0.0033);Gain of phosphorylation at D124 (P = 0.0033);

MVP

0.18

MPC

1.7

ClinPred

0.20

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.55

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.

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