chr4-744617-G-T

Variant names:

• chr4-744617-G-T
• rs1456214840
• NM_006315.7:c.391G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006315.7(PCGF3):​c.391G>T​(p.Asp131Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000782 in 1,406,520 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D131N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: PCGF3 NM_006315.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.53
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34739128).

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.391G>T	p.Asp131Tyr	missense	Exon 8 of 11	NP_006306.2
	PCGF3	NM_001317836.3		c.391G>T	p.Asp131Tyr	missense	Exon 9 of 12	NP_001304765.1	Q3KNV8-1
	PCGF3	NM_001395245.1		c.391G>T	p.Asp131Tyr	missense	Exon 9 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.391G>T	p.Asp131Tyr	missense	Exon 8 of 11	ENSP00000354724.5	Q3KNV8-1
	PCGF3	ENST00000470161.6	TSL:1	c.391G>T	p.Asp131Tyr	missense	Exon 8 of 11	ENSP00000420489.2	Q3KNV8-1
	PCGF3	ENST00000870362.1		c.391G>T	p.Asp131Tyr	missense	Exon 9 of 12	ENSP00000540421.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000782 AC: 11 AN: 1406520 Hom.: 0 Cov.: 31 AF XY: 0.0000130 AC XY: 9 AN XY: 694564

African (AFR) AF: 0.00 AC: 0 AN: 31888

American (AMR) AF: 0.00 AC: 0 AN: 36692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25264

East Asian (EAS) AF: 0.00 AC: 0 AN: 36320

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000831 AC: 9 AN: 1082888

Other (OTH) AF: 0.0000172 AC: 1 AN: 58300

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Benign	0.041
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.010	D
Polyphen		0.20	B
Vest4		0.55
MutPred		0.18		Gain of glycosylation at S132 (P = 0.0085)
MVP		0.56
MPC		1.1
ClinPred		0.89	D
GERP RS		4.4
Varity_R		0.17
gMVP		0.55
Mutation Taster		=65/35	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: rs1456214840; hg19: chr4-738405;