10-103345028-T-G

Position:

chr10-103345028-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001011663.2(PCGF6):c.778A>C(p.Ile260Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000138 in 1,590,608 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

PCGF6
NM_001011663.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0866864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PCGF6	NM_001011663.2 linkuse as main transcript	c.778A>C	p.Ile260Leu	missense_variant	6/10	ENST00000369847.4	NP_001011663.1
PCGF6	XM_047425832.1 linkuse as main transcript	c.778A>C	p.Ile260Leu	missense_variant	6/8		XP_047281788.1
PCGF6	NM_032154.4 linkuse as main transcript	c.557+3688A>C		intron_variant			NP_115530.2
PCGF6	XM_047425834.1 linkuse as main transcript			downstream_gene_variant			XP_047281790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCGF6	ENST00000369847.4 linkuse as main transcript	c.778A>C	p.Ile260Leu	missense_variant	6/10	1	NM_001011663.2	ENSP00000358862	P1	Q9BYE7-1
PCGF6	ENST00000337211.8 linkuse as main transcript	c.557+3688A>C		intron_variant		1		ENSP00000338845		Q9BYE7-3
PCGF6	ENST00000490296.1 linkuse as main transcript	n.815A>C		non_coding_transcript_exon_variant	6/10	2
PCGF6	ENST00000647574.1 linkuse as main transcript	c.*38+2210A>C		intron_variant, NMD_transcript_variant				ENSP00000497672

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

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

GnomAD3 exomes

AF:

0.0000247

AC:

AN:

242636

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130956

show subpopulations

Gnomad AFR exome

AF:

0.000373

Gnomad AMR exome

AF:

0.00

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:

0.00000417

AC:

AN:

1438414

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716244

show subpopulations

Gnomad4 AFR exome

AF:

0.000184

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000105

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000386

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

Alfa

AF:

0.0000659

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

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

Jun 13, 2024

The c.778A>C (p.I260L) alteration is located in exon 6 (coding exon 6) of the PCGF6 gene. This alteration results from a A to C substitution at nucleotide position 778, causing the isoleucine (I) at amino acid position 260 to be replaced by a leucine (L). 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

0.21

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.023

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.090

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

M_CAP

Benign

0.0061

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.025

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.56

REVEL

Benign

0.040

Sift

Benign

0.50

Sift4G

Benign

0.81

Polyphen

0.034

Vest4

0.49

MVP

0.38

MPC

0.35

ClinPred

0.097

GERP RS

4.5

Varity_R

0.11

gMVP

0.22

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