10-103345062-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001011663.2(PCGF6):ā€‹c.744A>Gā€‹(p.Pro248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,612,710 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00090 ( 1 hom., cov: 32)
Exomes š‘“: 0.0019 ( 0 hom. )

Consequence

PCGF6
NM_001011663.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.524
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 10-103345062-T-C is Benign according to our data. Variant chr10-103345062-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 719987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.524 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCGF6NM_001011663.2 linkuse as main transcriptc.744A>G p.Pro248= synonymous_variant 6/10 ENST00000369847.4 NP_001011663.1
PCGF6XM_047425832.1 linkuse as main transcriptc.744A>G p.Pro248= synonymous_variant 6/8 XP_047281788.1
PCGF6XM_047425834.1 linkuse as main transcriptc.*31A>G 3_prime_UTR_variant 4/4 XP_047281790.1
PCGF6NM_032154.4 linkuse as main transcriptc.557+3654A>G intron_variant NP_115530.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PCGF6ENST00000369847.4 linkuse as main transcriptc.744A>G p.Pro248= synonymous_variant 6/101 NM_001011663.2 ENSP00000358862 P1Q9BYE7-1
PCGF6ENST00000337211.8 linkuse as main transcriptc.557+3654A>G intron_variant 1 ENSP00000338845 Q9BYE7-3
PCGF6ENST00000490296.1 linkuse as main transcriptn.781A>G non_coding_transcript_exon_variant 6/102
PCGF6ENST00000647574.1 linkuse as main transcriptc.*38+2176A>G intron_variant, NMD_transcript_variant ENSP00000497672

Frequencies

GnomAD3 genomes
AF:
0.000900
AC:
137
AN:
152162
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000458
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00113
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00140
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000853
AC:
214
AN:
250920
Hom.:
0
AF XY:
0.000951
AC XY:
129
AN XY:
135624
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.000895
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000601
Gnomad NFE exome
AF:
0.00153
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00189
AC:
2759
AN:
1460430
Hom.:
0
Cov.:
29
AF XY:
0.00180
AC XY:
1308
AN XY:
726570
show subpopulations
Gnomad4 AFR exome
AF:
0.0000898
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00103
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000993
Gnomad4 NFE exome
AF:
0.00234
Gnomad4 OTH exome
AF:
0.00111
GnomAD4 genome
AF:
0.000900
AC:
137
AN:
152280
Hom.:
1
Cov.:
32
AF XY:
0.000846
AC XY:
63
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.000457
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00113
Gnomad4 NFE
AF:
0.00140
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00143
Hom.:
0
Bravo
AF:
0.000790
EpiCase
AF:
0.00115
EpiControl
AF:
0.00154

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
9.1
DANN
Benign
0.73

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.

Other links and lift over

dbSNP: rs61760880; hg19: chr10-105104819; API