4-761356-G-C

Variant names:

• chr4-761356-G-C
• rs141712126
• NM_006315.7:c.540G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006315.7(PCGF3):​c.540G>C​(p.Ala180Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,068 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. Synonymous variant affecting the same amino acid position (i.e. A180A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: PCGF3 NM_006315.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967
• Publications: 0 publications found

Genes affected

PCGF3 (HGNC:10066): (polycomb group ring finger 3) The protein encoded by this gene contains a C3HC4 type RING finger, which is a motif known to be involved in protein-protein interactions. The specific function of this protein has not yet been determined. [provided by RefSeq, Jul 2008]

LOC124900163 (HGNC:):

PCGF3-AS1 (HGNC:56108): (PCGF3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.967 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006315.7. 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
	PCGF3	NM_006315.7	MANE Select	c.540G>C	p.Ala180Ala	synonymous	Exon 9 of 11	NP_006306.2
	PCGF3	NM_001317836.3		c.540G>C	p.Ala180Ala	synonymous	Exon 10 of 12	NP_001304765.1	Q3KNV8-1
	PCGF3	NM_001395245.1		c.540G>C	p.Ala180Ala	synonymous	Exon 10 of 12	NP_001382174.1	Q3KNV8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF3	ENST00000362003.10	TSL:5 MANE Select	c.540G>C	p.Ala180Ala	synonymous	Exon 9 of 11	ENSP00000354724.5	Q3KNV8-1
	PCGF3	ENST00000470161.6	TSL:1	c.540G>C	p.Ala180Ala	synonymous	Exon 9 of 11	ENSP00000420489.2	Q3KNV8-1
	PCGF3	ENST00000870362.1		c.540G>C	p.Ala180Ala	synonymous	Exon 10 of 12	ENSP00000540421.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000805 AC: 2 AN: 248394 AF XY: 0.0000148

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: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460068 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726076

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 85998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110976

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000164 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.35
DANN	Benign	0.76
PhyloP100		-0.97

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: rs141712126; hg19: chr4-755144;