chr10-103345069-C-T

Position:

chr10-103345069-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000369847.4(PCGF6):c.737G>A(p.Arg246His) variant causes a missense change. The variant allele was found at a frequency of 0.000148 in 1,613,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

PCGF6
ENST00000369847.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

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:

PCGF6 (HGNC:):

PCGF6 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0130927265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCGF6	NM_001011663.2 linkuse as main transcript	c.737G>A	p.Arg246His	missense_variant	6/10	ENST00000369847.4	NP_001011663.1	Q9BYE7-1
PCGF6	XM_047425832.1 linkuse as main transcript	c.737G>A	p.Arg246His	missense_variant	6/8		XP_047281788.1
PCGF6	XM_047425834.1 linkuse as main transcript	c.*24G>A		3_prime_UTR_variant	4/4		XP_047281790.1
PCGF6	NM_032154.4 linkuse as main transcript	c.557+3647G>A		intron_variant			NP_115530.2	Q9BYE7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCGF6	ENST00000369847.4 linkuse as main transcript	c.737G>A	p.Arg246His	missense_variant	6/10	1	NM_001011663.2	ENSP00000358862.3	Q9BYE7-1
PCGF6	ENST00000337211.8 linkuse as main transcript	c.557+3647G>A		intron_variant		1		ENSP00000338845.4	Q9BYE7-3
PCGF6	ENST00000490296.1 linkuse as main transcript	n.774G>A		non_coding_transcript_exon_variant	6/10	2
PCGF6	ENST00000647574.1 linkuse as main transcript	n.*38+2169G>A		intron_variant				ENSP00000497672.1	A0A3B3ISZ4

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000231

AC:

AN:

251092

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00467

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000144

AC:

211

AN:

1460918

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

121

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00559

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000178

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000625

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

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

Jan 19, 2022

The c.737G>A (p.R246H) alteration is located in exon 6 (coding exon 6) of the PCGF6 gene. This alteration results from a G to A substitution at nucleotide position 737, causing the arginine (R) at amino acid position 246 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.029

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0094

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.23

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

1.7

REVEL

Benign

0.051

Sift

Benign

0.13

Sift4G

Benign

0.24

Polyphen

0.0020

Vest4

0.57

MVP

0.45

MPC

0.44

ClinPred

0.031

GERP RS

3.8

Varity_R

0.045

gMVP

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

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