17-38735257-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007144.3(PCGF2):c.1001C>A(p.Thr334Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,462,408 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

PCGF2
NM_007144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.68

Variant links:

Genes affected

PCGF2 (HGNC:12929): (polycomb group ring finger 2) The protein encoded by this gene contains a RING finger motif and is similar to the polycomb group (PcG) gene products. PcG gene products form complexes via protein-protein interaction and maintain the transcription repression of genes involved in embryogenesis, cell cycles, and tumorigenesis. This protein was shown to act as a negative regulator of transcription and has tumor suppressor activity. The expression of this gene was detected in various tumor cells, but is limited in neural organs in normal tissues. Knockout studies in mice suggested that this protein may negatively regulate the expression of different cytokines, chemokines, and chemokine receptors, and thus plays an important role in lymphocyte differentiation and migration, as well as in immune responses. [provided by RefSeq, Jul 2008]

PCGF2 links:

CISD3 (HGNC:27578): (CDGSH iron sulfur domain 3) CISD3 is a member of the CDGSH domain-containing family, which may play a role in regulating electron transport and oxidative phosphorylation (Wiley et al., 2007 [PubMed 17376863]).[supplied by OMIM, Apr 2008]

CISD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.21483228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCGF2	NM_007144.3 linkuse as main transcript	c.1001C>A	p.Thr334Asn	missense_variant	11/11	ENST00000620225.5
CISD3	NM_001136498.2 linkuse as main transcript	c.*1802G>T		3_prime_UTR_variant	4/4	ENST00000613478.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCGF2	ENST00000620225.5 linkuse as main transcript	c.1001C>A	p.Thr334Asn	missense_variant	11/11	1	NM_007144.3	P1
CISD3	ENST00000613478.2 linkuse as main transcript	c.*1802G>T		3_prime_UTR_variant	4/4	2	NM_001136498.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

7.63e-7

AC:

AN:

1310224

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

635838

show subpopulations

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:

9.72e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00143

Bravo

AF:

0.00000378

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

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Feb 26, 2024

Variant summary: PCGF2 c.1001C>A (p.Thr334Asn) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 130138 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1001C>A in individuals affected with Turnpenny-Fry Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.0033

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.78

Sift4G

Benign

0.14

T;T;T

Polyphen

0.82

P;P;P

Vest4

0.38

MutPred

0.086

Loss of phosphorylation at T334 (P = 0.0166);Loss of phosphorylation at T334 (P = 0.0166);Loss of phosphorylation at T334 (P = 0.0166);

MVP

0.42

ClinPred

0.86

GERP RS

5.2

Varity_R

0.15

gMVP

0.31

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