9-120869767-A-G

Variant names:

• chr9-120869767-A-G
• rs1056567
• ENST00000312189.10:c.543T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000312189.10(PHF19):​c.543T>C​(p.Ser181Ser) 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
• Publications: 46 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000312189.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF19	NM_015651.3	MANE Select	c.465+78T>C		intron	N/A	NP_056466.1
	PHF19	NM_001009936.3		c.543T>C	p.Ser181Ser	synonymous	Exon 5 of 5	NP_001009936.1
	PHF19	NM_001286843.2		c.*136T>C		3_prime_UTR	Exon 5 of 5	NP_001273772.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF19	ENST00000312189.10	TSL:1	c.543T>C	p.Ser181Ser	synonymous	Exon 5 of 5	ENSP00000310372.6
	PHF19	ENST00000373896.8	TSL:2 MANE Select	c.465+78T>C		intron	N/A	ENSP00000363003.3
	PHF19	ENST00000616568.5	TSL:1	c.522+78T>C		intron	N/A	ENSP00000483946.1

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

GnomAD2 exomes AF: 0.692 AC: 156341 AN: 226018 AF XY: 0.696

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 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

African (AFR) AF: 0.558 AC: 18622 AN: 33346

American (AMR) AF: 0.826 AC: 35347 AN: 42780

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 19519 AN: 25782

East Asian (EAS) AF: 0.450 AC: 17672 AN: 39302

South Asian (SAS) AF: 0.798 AC: 66670 AN: 83580

European-Finnish (FIN) AF: 0.627 AC: 32793 AN: 52310

Middle Eastern (MID) AF: 0.741 AC: 4261 AN: 5750

European-Non Finnish (NFE) AF: 0.680 AC: 752117 AN: 1105478

Other (OTH) AF: 0.684 AC: 41002 AN: 59902

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

African (AFR) AF: 0.567 AC: 23335 AN: 41124

American (AMR) AF: 0.776 AC: 11819 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2659 AN: 3468

East Asian (EAS) AF: 0.506 AC: 2566 AN: 5072

South Asian (SAS) AF: 0.786 AC: 3762 AN: 4784

European-Finnish (FIN) AF: 0.621 AC: 6474 AN: 10420

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 45944 AN: 67842

Other (OTH) AF: 0.683 AC: 1431 AN: 2096

Alfa AF: 0.680 Hom.: 55430

Bravo AF: 0.657

Asia WGS AF: 0.646 AC: 2246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.54
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1056567; hg19: chr9-123632045; COSMIC: COSV56488955; COSMIC: COSV56488955;