chr4-765023-C-T

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006315.7(PCGF3):​c.640C>T​(p.His214Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PCGF3
NM_006315.7 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.24
Variant links:
Genes affected
PCGF3 (HGNC:10066): (polycomb group ring finger 3) The protein encoded by this gene contains a C3HC4 type RING finger, which is a motif known to be involved in protein-protein interactions. The specific function of this protein has not yet been determined. [provided by RefSeq, Jul 2008]
PCGF3-AS1 (HGNC:56108): (PCGF3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PCGF3NM_006315.7 linkuse as main transcriptc.640C>T p.His214Tyr missense_variant 10/11 ENST00000362003.10
LOC124900163XM_047416474.1 linkuse as main transcriptc.-2693-2283G>A intron_variant
PCGF3-AS1NR_171661.1 linkuse as main transcriptn.103G>A non_coding_transcript_exon_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PCGF3ENST00000362003.10 linkuse as main transcriptc.640C>T p.His214Tyr missense_variant 10/115 NM_006315.7 P1Q3KNV8-1
ENST00000454037.1 linkuse as main transcriptn.52G>A non_coding_transcript_exon_variant 1/25
PCGF3-AS1ENST00000660016.1 linkuse as main transcriptn.79-2283G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

See cases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaOct 10, 2018This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
D;D
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
.;D
M_CAP
Benign
0.016
T
MetaRNN
Pathogenic
0.82
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.89
L;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-3.9
D;D
REVEL
Uncertain
0.34
Sift
Benign
0.057
T;T
Sift4G
Benign
0.31
T;T
Polyphen
1.0
D;D
Vest4
0.87
MutPred
0.60
Loss of methylation at K217 (P = 0.0448);Loss of methylation at K217 (P = 0.0448);
MVP
0.55
MPC
2.1
ClinPred
0.98
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.59
gMVP
0.93

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: rs1745284197; hg19: chr4-758811; API