10-103315955-C-T

Variant names:

• chr10-103315955-C-T
• rs12220267
• NM_001011663.2:c.910-1683G>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.910-1683G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 149,676 control chromosomes in the GnomAD database, including 6,567 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 0.27 (6567 hom., cov: 29)
• Consequence: PCGF6 NM_001011663.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716
• Publications: 16 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011663.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF6	NM_001011663.2	MANE Select	c.910-1683G>A		intron	N/A	NP_001011663.1
	PCGF6	NM_032154.4		c.685-1683G>A		intron	N/A	NP_115530.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF6	ENST00000369847.4	TSL:1 MANE Select	c.910-1683G>A		intron	N/A	ENSP00000358862.3
	PCGF6	ENST00000337211.8	TSL:1	c.685-1683G>A		intron	N/A	ENSP00000338845.4
	PCGF6	ENST00000490296.1	TSL:2	n.947-1683G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.272 AC: 40712 AN: 149572 Hom.: 6564 Cov.: 29

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.272 AC: 40715 AN: 149676 Hom.: 6567 Cov.: 29 AF XY: 0.279 AC XY: 20366 AN XY: 72928

African (AFR) AF: 0.0942 AC: 3797 AN: 40318

American (AMR) AF: 0.299 AC: 4466 AN: 14940

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1064 AN: 3464

East Asian (EAS) AF: 0.347 AC: 1768 AN: 5100

South Asian (SAS) AF: 0.503 AC: 2395 AN: 4758

European-Finnish (FIN) AF: 0.407 AC: 4111 AN: 10110

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22245 AN: 67714

Other (OTH) AF: 0.279 AC: 579 AN: 2076

Alfa AF: 0.253 Hom.: 1050

Bravo AF: 0.250

Asia WGS AF: 0.390 AC: 1352 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.52
PhyloP100		0.72
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: rs12220267; hg19: chr10-105075712;