10-103315955-C-T

Position:

• chr10-103315955-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCGF6	NM_001011663.2	c.910-1683G>A		intron_variant		ENST00000369847.4	NP_001011663.1
PCGF6	NM_032154.4	c.685-1683G>A		intron_variant			NP_115530.2
PCGF6	XM_047425832.1	c.*45-1683G>A		intron_variant			XP_047281788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCGF6	ENST00000369847.4	c.910-1683G>A		intron_variant		1	NM_001011663.2	ENSP00000358862.3
PCGF6	ENST00000337211.8	c.685-1683G>A		intron_variant		1		ENSP00000338845.4
PCGF6	ENST00000490296.1	n.947-1683G>A		intron_variant		2
PCGF6	ENST00000647574.1	n.*551-1683G>A		intron_variant				ENSP00000497672.1

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

Gnomad4 AFR AF: 0.0942

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.279

Alfa AF: 0.258 Hom.: 1047

Bravo AF: 0.250

Asia WGS AF: 0.390 AC: 1352 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs12220267; hg19: chr10-105075712;