chr9-120869767-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000312189.10(PHF19):​c.543T>G​(p.Ser181Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHF19 ENST00000312189.10 missense
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06575379).

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>G		intron	N/A	NP_056466.1
	PHF19	NM_001009936.3		c.543T>G	p.Ser181Arg	missense	Exon 5 of 5	NP_001009936.1
	PHF19	NM_001286843.2		c.*136T>G		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>G	p.Ser181Arg	missense	Exon 5 of 5	ENSP00000310372.6
	PHF19	ENST00000373896.8	TSL:2 MANE Select	c.465+78T>G		intron	N/A	ENSP00000363003.3
	PHF19	ENST00000616568.5	TSL:1	c.522+78T>G		intron	N/A	ENSP00000483946.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448590 Hom.: 0 Cov.: 52 AF XY: 0.00 AC XY: 0 AN XY: 718996

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 42802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25782

East Asian (EAS) AF: 0.00 AC: 0 AN: 39312

South Asian (SAS) AF: 0.00 AC: 0 AN: 83594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105728

Other (OTH) AF: 0.00 AC: 0 AN: 59920

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 55430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.22
DANN	Benign	0.81
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.1
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.052
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.14
MutPred		0.15		Loss of ubiquitination at K185 (P = 0.0184)
MVP		0.043
ClinPred		0.087	T
GERP RS		-3.0
Mutation Taster		=100/0	polymorphism

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;