NM_007144.3:c.1021C>T

Variant names:

• chr17-38735237-G-A
• rs1208938665
• NM_007144.3:c.1021C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_007144.3(PCGF2):​c.1021C>T​(p.Pro341Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,441,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: PCGF2 NM_007144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.393
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.084166706).
• BS2: High AC in GnomAdExome4 at 29 AD gene.

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.1021C>T	p.Pro341Ser	missense	Exon 11 of 11	NP_009075.1	P35227
	CISD3	NM_001136498.2	MANE Select	c.*1782G>A		3_prime_UTR	Exon 4 of 4	NP_001129970.1	P0C7P0
	PCGF2	NM_001369614.1		c.1021C>T	p.Pro341Ser	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.1021C>T	p.Pro341Ser	missense	Exon 11 of 11	ENSP00000482815.1	P35227
	PCGF2	ENST00000611883.4	TSL:1	c.1021C>T	p.Pro341Ser	missense	Exon 10 of 10	ENSP00000478970.1	P35227
	PCGF2	ENST00000616199.4	TSL:1	c.1021C>T	p.Pro341Ser	missense	Exon 12 of 12	ENSP00000482063.1	P35227

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152152 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

GnomAD4 exome AF: 0.0000225 AC: 29 AN: 1289002 Hom.: 0 Cov.: 33 AF XY: 0.0000320 AC XY: 20 AN XY: 624282

African (AFR) AF: 0.00 AC: 0 AN: 28880

American (AMR) AF: 0.00 AC: 0 AN: 23360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18562

East Asian (EAS) AF: 0.00 AC: 0 AN: 34114

South Asian (SAS) AF: 0.00 AC: 0 AN: 63008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5122

European-Non Finnish (NFE) AF: 0.0000285 AC: 29 AN: 1018680

Other (OTH) AF: 0.00 AC: 0 AN: 52862

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.067
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.33	N
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.075	N
PhyloP100		0.39
PrimateAI	Uncertain	0.52	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.020	B
Vest4		0.050
MVP		0.25
ClinPred		0.93	D
GERP RS		2.0
PromoterAI		-0.017	Neutral
Varity_R		0.043
gMVP		0.41
Mutation Taster		=97/3	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: rs1208938665; hg19: chr17-36891490;