17-38735234-G-T

Variant names:

• chr17-38735234-G-T
• rs775916672
• NM_007144.3:c.1024C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007144.3(PCGF2):​c.1024C>A​(p.Pro342Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,429,222 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P342R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: PCGF2 NM_007144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.335
• Publications: 1 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15960586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007144.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF2	NM_007144.3	MANE Select	c.1024C>A	p.Pro342Thr	missense	Exon 11 of 11	NP_009075.1	P35227
	CISD3	NM_001136498.2	MANE Select	c.*1779G>T		3_prime_UTR	Exon 4 of 4	NP_001129970.1	P0C7P0
	PCGF2	NM_001369614.1		c.1024C>A	p.Pro342Thr	missense	Exon 10 of 10	NP_001356543.1	P35227

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF2	ENST00000620225.5	TSL:1 MANE Select	c.1024C>A	p.Pro342Thr	missense	Exon 11 of 11	ENSP00000482815.1	P35227
	PCGF2	ENST00000611883.4	TSL:1	c.1024C>A	p.Pro342Thr	missense	Exon 10 of 10	ENSP00000478970.1	P35227
	PCGF2	ENST00000616199.4	TSL:1	c.1024C>A	p.Pro342Thr	missense	Exon 12 of 12	ENSP00000482063.1	P35227

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

GnomAD2 exomes AF: 0.0000122 AC: 1 AN: 81972 AF XY: 0.0000245

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000325

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000235 AC: 3 AN: 1277052 Hom.: 0 Cov.: 33 AF XY: 0.00000162 AC XY: 1 AN XY: 618026

African (AFR) AF: 0.0000352 AC: 1 AN: 28432

American (AMR) AF: 0.00 AC: 0 AN: 21622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18164

East Asian (EAS) AF: 0.0000295 AC: 1 AN: 33856

South Asian (SAS) AF: 0.00 AC: 0 AN: 60608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5088

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1013002

Other (OTH) AF: 0.0000191 AC: 1 AN: 52316

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74330

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.71	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.34
PrimateAI	Uncertain	0.58	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.76	P
Vest4		0.095
MutPred		0.12		Loss of catalytic residue at P341 (P = 0.0193)
MVP		0.47
ClinPred		0.32	T
GERP RS		5.2
PromoterAI		-0.090	Neutral
Varity_R		0.19
gMVP		0.41
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs775916672; hg19: chr17-36891487;