chr17-38735214-T-G

Variant names:

• chr17-38735214-T-G
• rs377749543
• NM_007144.3:c.*9A>C

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.*9A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,245,446 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: PCGF2 NM_007144.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• 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: 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 (BayesDel_noAF=-0.45).

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.*9A>C		3_prime_UTR	Exon 11 of 11	NP_009075.1	P35227
	CISD3	NM_001136498.2	MANE Select	c.*1759T>G		3_prime_UTR	Exon 4 of 4	NP_001129970.1	P0C7P0
	PCGF2	NM_001369614.1		c.*9A>C		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.*9A>C		3_prime_UTR	Exon 11 of 11	ENSP00000482815.1	P35227
	CISD3	ENST00000613478.2	TSL:2 MANE Select	c.*1759T>G		3_prime_UTR	Exon 4 of 4	ENSP00000483781.1	P0C7P0
	PCGF2	ENST00000611883.4	TSL:1	c.*9A>C		3_prime_UTR	Exon 10 of 10	ENSP00000478970.1	P35227

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000161 AC: 2 AN: 1245446 Hom.: 0 Cov.: 33 AF XY: 0.00000333 AC XY: 2 AN XY: 600888

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

African (AFR) AF: 0.00 AC: 0 AN: 27408

American (AMR) AF: 0.00 AC: 0 AN: 18444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17330

East Asian (EAS) AF: 0.00 AC: 0 AN: 32496

South Asian (SAS) AF: 0.00 AC: 0 AN: 54262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4906

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 997390

Other (OTH) AF: 0.00 AC: 0 AN: 50712

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.1
DANN	Benign	0.74
PhyloP100		-0.033
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs377749543; hg19: chr17-36891467;