chr17-38734696-T-C

Variant names:

• chr17-38734696-T-C
• rs708692
• NM_007144.3:c.*527A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007144.3(PCGF2):​c.*527A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,478 control chromosomes in the GnomAD database, including 17,665 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (17579 hom., cov: 31)
  • Exomes 𝑓: 0.50 (86 hom.)
• Consequence: PCGF2 NM_007144.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

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.*527A>G		3_prime_UTR	Exon 11 of 11	NP_009075.1	P35227
	CISD3	NM_001136498.2	MANE Select	c.*1241T>C		3_prime_UTR	Exon 4 of 4	NP_001129970.1	P0C7P0
	PCGF2	NM_001369614.1		c.*527A>G		3_prime_UTR	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.*527A>G		3_prime_UTR	Exon 11 of 11	ENSP00000482815.1	P35227
	CISD3	ENST00000613478.2	TSL:2 MANE Select	c.*1241T>C		3_prime_UTR	Exon 4 of 4	ENSP00000483781.1	P0C7P0
	PCGF2	ENST00000611883.4	TSL:1	c.*527A>G		3_prime_UTR	Exon 10 of 10	ENSP00000478970.1	P35227

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72562 AN: 151710 Hom.: 17555 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.500 AC: 325 AN: 650 Hom.: 86 Cov.: 0 AF XY: 0.505 AC XY: 194 AN XY: 384

African (AFR) AF: 0.500 AC: 5 AN: 10

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 3 AN: 8

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.537 AC: 232 AN: 432

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.444 AC: 79 AN: 178

Other (OTH) AF: 0.278 AC: 5 AN: 18

GnomAD4 genome AF: 0.478 AC: 72630 AN: 151828 Hom.: 17579 Cov.: 31 AF XY: 0.480 AC XY: 35600 AN XY: 74194

African (AFR) AF: 0.500 AC: 20693 AN: 41378

American (AMR) AF: 0.422 AC: 6438 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1448 AN: 5160

South Asian (SAS) AF: 0.479 AC: 2307 AN: 4816

European-Finnish (FIN) AF: 0.572 AC: 6018 AN: 10514

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32787 AN: 67914

Other (OTH) AF: 0.476 AC: 1006 AN: 2112

Alfa AF: 0.468 Hom.: 63056

Bravo AF: 0.464

Asia WGS AF: 0.431 AC: 1498 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.28
PhyloP100		-0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs708692; hg19: chr17-36890949;