rs2242235

Positions:

• chr4-761422-A-G
• chr4-761422-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006315.7(PCGF3):​c.600+6A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 1,596,662 control chromosomes in the GnomAD database, including 5,911 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 0.076 (504 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5407 hom.)
• Consequence: PCGF3 NM_006315.7 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00006706
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

Genes affected

LOC124900163 (HGNC:):

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124900163	XM_047416474.1	c.-1375T>C		5_prime_UTR_variant	2/2
PCGF3	NM_006315.7	c.600+6A>G		splice_donor_region_variant, intron_variant		ENST00000362003.10
PCGF3-AS1	NR_171661.1	n.3402T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCGF3	ENST00000362003.10	c.600+6A>G		splice_donor_region_variant, intron_variant		5	NM_006315.7	P1
PCGF3-AS1	ENST00000660016.1	n.1397T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11551 AN: 152232 Hom.: 504 Cov.: 33

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0834

Gnomad OTH AF: 0.0712

GnomAD3 exomes AF: 0.0913 AC: 21577 AN: 236314 Hom.: 1130 AF XY: 0.0942 AC XY: 12113 AN XY: 128592

Gnomad AFR exome AF: 0.0409

Gnomad AMR exome AF: 0.0976

Gnomad ASJ exome AF: 0.0938

Gnomad EAS exome AF: 0.0730

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.0813

Gnomad OTH exome AF: 0.0894

GnomAD4 exome AF: 0.0816 AC: 117908 AN: 1444312 Hom.: 5407 Cov.: 31 AF XY: 0.0843 AC XY: 60477 AN XY: 717006

Gnomad4 AFR exome AF: 0.0421

Gnomad4 AMR exome AF: 0.0946

Gnomad4 ASJ exome AF: 0.0956

Gnomad4 EAS exome AF: 0.0890

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0755

Gnomad4 OTH exome AF: 0.0855

GnomAD4 genome AF: 0.0759 AC: 11558 AN: 152350 Hom.: 504 Cov.: 33 AF XY: 0.0794 AC XY: 5918 AN XY: 74494

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.0824

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.0712

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0834

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0802 Hom.: 1017

Bravo AF: 0.0693

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000067
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2242235; hg19: chr4-755210; COSMIC: COSV62860610; COSMIC: COSV62860610;