10-103350930-G-A

Position:

• chr10-103350930-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000369847.4(PCGF6):​c.137C>T​(p.Ala46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCGF6 ENST00000369847.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

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

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=0.08564448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCGF6	NM_001011663.2	c.137C>T	p.Ala46Val	missense_variant	1/10	ENST00000369847.4	NP_001011663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCGF6	ENST00000369847.4	c.137C>T	p.Ala46Val	missense_variant	1/10	1	NM_001011663.2	ENSP00000358862	P1
PCGF6	ENST00000337211.8	c.137C>T	p.Ala46Val	missense_variant	1/7	1		ENSP00000338845
PCGF6	ENST00000490296.1	n.152C>T		non_coding_transcript_exon_variant	1/10	2
PCGF6	ENST00000647574.1	c.137C>T	p.Ala46Val	missense_variant, NMD_transcript_variant	1/10			ENSP00000497672

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1360118 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 672406

Gnomad4 AFR exome AF: 0.00

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 Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.137C>T (p.A46V) alteration is located in exon 1 (coding exon 1) of the PCGF6 gene. This alteration results from a C to T substitution at nucleotide position 137, causing the alanine (A) at amino acid position 46 to be replaced by a valine (V). 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	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	.;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.040
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.23	T;T
Polyphen		0.021	B;B
Vest4		0.085
MutPred		0.18		Loss of glycosylation at P45 (P = 0.1299);Loss of glycosylation at P45 (P = 0.1299);
MVP		0.30
MPC		0.28
ClinPred		0.19	T
GERP RS		1.6
Varity_R		0.091
gMVP		0.28

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: rs1592082146; hg19: chr10-105110687;