chr10-91227753-C-T

Variant names:

• chr10-91227753-C-T
• rs1057971
• NM_032373.5:c.112+4770C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032373.5. 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
	PCGF5	NM_032373.5	MANE Select	c.112+4770C>T		intron	N/A	NP_115749.2
	PCGF5	NM_001256549.2		c.112+4770C>T		intron	N/A	NP_001243478.1	Q86SE9-1
	PCGF5	NM_001257101.2		c.112+4770C>T		intron	N/A	NP_001244030.1	Q86SE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF5	ENST00000336126.6	TSL:1 MANE Select	c.112+4770C>T		intron	N/A	ENSP00000337500.5	Q86SE9-1
	PCGF5	ENST00000614189.4	TSL:1	c.112+4770C>T		intron	N/A	ENSP00000479492.1	Q86SE9-1
	PCGF5	ENST00000543648.5	TSL:2	c.112+4770C>T		intron	N/A	ENSP00000445704.1	Q86SE9-1

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

African (AFR) AF: 0.257 AC: 4098 AN: 15968

American (AMR) AF: 0.0370 AC: 93 AN: 2516

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 437 AN: 5532

East Asian (EAS) AF: 0.00166 AC: 7 AN: 4212

South Asian (SAS) AF: 0.0762 AC: 1412 AN: 18540

European-Finnish (FIN) AF: 0.0439 AC: 38 AN: 866

Middle Eastern (MID) AF: 0.109 AC: 184 AN: 1686

European-Non Finnish (NFE) AF: 0.0506 AC: 38972 AN: 770490

Other (OTH) AF: 0.0678 AC: 1903 AN: 28054

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

African (AFR) AF: 0.247 AC: 10231 AN: 41370

American (AMR) AF: 0.0570 AC: 870 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0907 AC: 315 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5184

South Asian (SAS) AF: 0.0707 AC: 340 AN: 4810

European-Finnish (FIN) AF: 0.0690 AC: 731 AN: 10600

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0558 AC: 3794 AN: 67954

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.0710 Hom.: 770

Bravo AF: 0.112

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1057971; hg19: chr10-92987510;