rs1057971

Positions:

• chr10-91227753-C-T

Variant summary

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

The NM_032373.5(PCGF5):​c.112+4770C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 999,840 control chromosomes in the GnomAD database, including 3,302 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 0.11 (1559 hom., cov: 32)
  • Exomes 𝑓: 0.056 (1743 hom.)
• Consequence: PCGF5 NM_032373.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

Genes affected

PCGF5 (HGNC:28264): (polycomb group ring finger 5) Predicted to enable metal ion binding activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; centrosome; and nucleoplasm. Part of PcG protein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCGF5	NM_032373.5	c.112+4770C>T		intron_variant		ENST00000336126.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCGF5	ENST00000336126.6	c.112+4770C>T		intron_variant		1	NM_032373.5	P1
PCGF5	ENST00000614189.4	c.112+4770C>T		intron_variant		1		P1
PCGF5	ENST00000543648.5	c.112+4770C>T		intron_variant		2		P1
PCGF5	ENST00000490164.1	n.766C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16558 AN: 151858 Hom.: 1555 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.0907

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0558

Gnomad OTH AF: 0.0962

GnomAD4 exome AF: 0.0556 AC: 47144 AN: 847864 Hom.: 1743 Cov.: 29 AF XY: 0.0551 AC XY: 21637 AN XY: 392708

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.0370

Gnomad4 ASJ exome AF: 0.0790

Gnomad4 EAS exome AF: 0.00166

Gnomad4 SAS exome AF: 0.0762

Gnomad4 FIN exome AF: 0.0439

Gnomad4 NFE exome AF: 0.0506

Gnomad4 OTH exome AF: 0.0678

GnomAD4 genome AF: 0.109 AC: 16573 AN: 151976 Hom.: 1559 Cov.: 32 AF XY: 0.108 AC XY: 8024 AN XY: 74328

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.0907

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0707

Gnomad4 FIN AF: 0.0690

Gnomad4 NFE AF: 0.0558

Gnomad4 OTH AF: 0.0952

Alfa AF: 0.0633 Hom.: 429

Bravo AF: 0.112

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.49
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

Publications

LitVar

Other links and lift over

dbSNP: rs1057971; hg19: chr10-92987510;