NM_006315.7:c.540G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006315.7(PCGF3):​c.540G>A​(p.Ala180Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,612,392 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00058 (9 hom.)
• Consequence: PCGF3 NM_006315.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 4-761356-G-A is Benign according to our data. Variant chr4-761356-G-A is described in ClinVar as Benign. ClinVar VariationId is 785081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.967 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00583 (888/152324) while in subpopulation AFR AF = 0.0205 (853/41572). AF 95% confidence interval is 0.0194. There are 5 homozygotes in GnomAd4. There are 421 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 gene

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>A	p.Ala180Ala	synonymous	Exon 9 of 11	NP_006306.2
	PCGF3	NM_001317836.3		c.540G>A	p.Ala180Ala	synonymous	Exon 10 of 12	NP_001304765.1	Q3KNV8-1
	PCGF3	NM_001395245.1		c.540G>A	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>A	p.Ala180Ala	synonymous	Exon 9 of 11	ENSP00000354724.5	Q3KNV8-1
	PCGF3	ENST00000470161.6	TSL:1	c.540G>A	p.Ala180Ala	synonymous	Exon 9 of 11	ENSP00000420489.2	Q3KNV8-1
	PCGF3	ENST00000870362.1		c.540G>A	p.Ala180Ala	synonymous	Exon 10 of 12	ENSP00000540421.1

Frequencies

GnomAD3 genomes AF: 0.00581 AC: 884 AN: 152206 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

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: 0.00287

GnomAD2 exomes AF: 0.00143 AC: 356 AN: 248394 AF XY: 0.00100

Gnomad AFR exome AF: 0.0210

Gnomad AMR exome AF: 0.000762

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000665

GnomAD4 exome AF: 0.000579 AC: 845 AN: 1460068 Hom.: 9 Cov.: 31 AF XY: 0.000475 AC XY: 345 AN XY: 726076

African (AFR) AF: 0.0215 AC: 720 AN: 33438

American (AMR) AF: 0.000786 AC: 35 AN: 44550

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

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39602

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 85998

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

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110976

Other (OTH) AF: 0.00128 AC: 77 AN: 60336

GnomAD4 genome AF: 0.00583 AC: 888 AN: 152324 Hom.: 5 Cov.: 33 AF XY: 0.00565 AC XY: 421 AN XY: 74484

African (AFR) AF: 0.0205 AC: 853 AN: 41572

American (AMR) AF: 0.00190 AC: 29 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00203 Hom.: 2

Bravo AF: 0.00649

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.3
DANN	Benign	0.91
PhyloP100		-0.97
Mutation Taster		=100/0	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: rs141712126; hg19: chr4-755144;