9-120869767-A-G

Position:

• chr9-120869767-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000312189.10(PHF19):​c.543T>C​(p.Ser181=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,599,464 control chromosomes in the GnomAD database, including 372,714 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 0.65 (32546 hom., cov: 28)
  • Exomes 𝑓: 0.68 (340168 hom.)
• Consequence: PHF19 ENST00000312189.10 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

Genes affected

PHF19 (HGNC:24566): (PHD finger protein 19) Enables methylated histone binding activity. Involved in positive regulation of histone H3-K27 methylation. Colocalizes with ESC/E(Z) complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-2.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF19	NM_015651.3	c.465+78T>C		intron_variant		ENST00000373896.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF19	ENST00000312189.10	c.543T>C	p.Ser181=	synonymous_variant	5/5	1
PHF19	ENST00000373896.8	c.465+78T>C		intron_variant		2	NM_015651.3	P1
PHF19	ENST00000616568.5	c.522+78T>C		intron_variant		1
PHF19	ENST00000436309.5	c.465+78T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98549 AN: 151116 Hom.: 32506 Cov.: 28

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.683

GnomAD3 exomes AF: 0.692 AC: 156341 AN: 226018 Hom.: 55040 AF XY: 0.696 AC XY: 84671 AN XY: 121694

Gnomad AFR exome AF: 0.559

Gnomad AMR exome AF: 0.837

Gnomad ASJ exome AF: 0.766

Gnomad EAS exome AF: 0.506

Gnomad SAS exome AF: 0.795

Gnomad FIN exome AF: 0.616

Gnomad NFE exome AF: 0.674

Gnomad OTH exome AF: 0.691

GnomAD4 exome AF: 0.682 AC: 988003 AN: 1448230 Hom.: 340168 Cov.: 52 AF XY: 0.686 AC XY: 493260 AN XY: 718842

Gnomad4 AFR exome AF: 0.558

Gnomad4 AMR exome AF: 0.826

Gnomad4 ASJ exome AF: 0.757

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.798

Gnomad4 FIN exome AF: 0.627

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.684

GnomAD4 genome AF: 0.652 AC: 98641 AN: 151234 Hom.: 32546 Cov.: 28 AF XY: 0.656 AC XY: 48395 AN XY: 73804

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.786

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.683

Alfa AF: 0.681 Hom.: 45467

Bravo AF: 0.657

Asia WGS AF: 0.646 AC: 2246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1056567; hg19: chr9-123632045; COSMIC: COSV56488955; COSMIC: COSV56488955;