NM_001011663.2:c.782+3080G>A

Variant names:

• chr10-103341944-C-T
• rs11191659
• NM_001011663.2:c.782+3080G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001011663.2(PCGF6):​c.782+3080G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 149,212 control chromosomes in the GnomAD database, including 1,404 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 0.12 (1404 hom., cov: 30)
• Consequence: PCGF6 NM_001011663.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCGF6	NM_001011663.2	c.782+3080G>A		intron_variant	Intron 6 of 9	ENST00000369847.4	NP_001011663.1
PCGF6	NM_032154.4	c.557+6772G>A		intron_variant	Intron 3 of 6		NP_115530.2
PCGF6	XM_047425832.1	c.782+3080G>A		intron_variant	Intron 6 of 7		XP_047281788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCGF6	ENST00000369847.4	c.782+3080G>A		intron_variant	Intron 6 of 9	1	NM_001011663.2	ENSP00000358862.3
PCGF6	ENST00000337211.8	c.557+6772G>A		intron_variant	Intron 3 of 6	1		ENSP00000338845.4
PCGF6	ENST00000490296.1	n.819+3080G>A		intron_variant	Intron 6 of 9	2
PCGF6	ENST00000647574.1	n.*39-2175G>A		intron_variant	Intron 4 of 9			ENSP00000497672.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18160 AN: 149112 Hom.: 1403 Cov.: 30

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0974

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18155 AN: 149212 Hom.: 1404 Cov.: 30 AF XY: 0.119 AC XY: 8704 AN XY: 72886

African (AFR) AF: 0.0374 AC: 1522 AN: 40694

American (AMR) AF: 0.104 AC: 1541 AN: 14872

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 629 AN: 3424

East Asian (EAS) AF: 0.134 AC: 678 AN: 5068

South Asian (SAS) AF: 0.0553 AC: 259 AN: 4684

European-Finnish (FIN) AF: 0.150 AC: 1528 AN: 10204

Middle Eastern (MID) AF: 0.0938 AC: 27 AN: 288

European-Non Finnish (NFE) AF: 0.172 AC: 11518 AN: 67044

Other (OTH) AF: 0.130 AC: 265 AN: 2034

Alfa AF: 0.146 Hom.: 1541

Bravo AF: 0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.75
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11191659; hg19: chr10-105101701;