Variant 10-103326608-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001011663.2(PCGF6):c.835G>A(p.Val279Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,672 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: 0.0000014 ( 0 hom. )

Consequence

PCGF6
NM_001011663.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

Variant links:

Genes affected

PCGF6 (HGNC:21156): (polycomb group ring finger 6) The protein encoded by this gene contains a RING finger motif, which is most closely related to those of polycomb group (PcG) proteins RNF110/MEL-18 and BMI1. PcG proteins are known to form protein complexes and function as transcription repressors. This protein has been shown to interact with some PcG proteins and act as a transcription repressor. The activity of this protein is found to be regulated by cell cycle dependent phosphorylation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PCGF6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PCGF6	NM_001011663.2 linkuse as main transcript	c.835G>A	p.Val279Ile	missense_variant	8/10	ENST00000369847.4	NP_001011663.1
PCGF6	NM_032154.4 linkuse as main transcript	c.610G>A	p.Val204Ile	missense_variant	5/7		NP_115530.2
PCGF6	XM_047425832.1 linkuse as main transcript	c.807G>A	p.Glu269=	synonymous_variant	7/8		XP_047281788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCGF6	ENST00000369847.4 linkuse as main transcript	c.835G>A	p.Val279Ile	missense_variant	8/10	1	NM_001011663.2	ENSP00000358862	P1	Q9BYE7-1
PCGF6	ENST00000337211.8 linkuse as main transcript	c.610G>A	p.Val204Ile	missense_variant	5/7	1		ENSP00000338845		Q9BYE7-3
PCGF6	ENST00000490296.1 linkuse as main transcript	n.872G>A		non_coding_transcript_exon_variant	8/10	2
PCGF6	ENST00000647574.1 linkuse as main transcript	c.*476G>A		3_prime_UTR_variant, NMD_transcript_variant	8/10			ENSP00000497672

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456672

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724502

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

May 13, 2024

The c.835G>A (p.V279I) alteration is located in exon 8 (coding exon 8) of the PCGF6 gene. This alteration results from a G to A substitution at nucleotide position 835, causing the valine (V) at amino acid position 279 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

.;T

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-0.58

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.22

Sift

Uncertain

0.014

D;D

Sift4G

Benign

0.45

T;T

Polyphen

0.99

D;D

Vest4

0.36

MutPred

0.76

.;Gain of loop (P = 0.0435);

MVP

0.63

MPC

0.23

ClinPred

0.98

GERP RS

5.0

Varity_R

0.16

gMVP

0.26

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.

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