PHF19 p.Ser181Arg

Variant names:

• chr9-120869769-T-G
• ENST00000312189.10:c.541A>C
• PHF19 p.Ser181Arg

Your query was ambiguous. Multiple possible variants found:

• chr9-120869769-T-G
• chr9-120869767-A-T
• chr9-120869767-A-C
• chr9-120869767-ACT-GCG
• chr9-120869767-ACT-TCG
• chr9-120869767-ACT-CCG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009936.3(PHF19):​c.541A>C​(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: 32)
• Consequence: PHF19 NM_001009936.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07734901).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009936.3. 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
	PHF19	NM_015651.3	MANE Select	c.465+76A>C		intron	N/A	NP_056466.1	Q5T6S3-1
	PHF19	NM_001009936.3		c.541A>C	p.Ser181Arg	missense	Exon 5 of 5	NP_001009936.1	Q5T6S3-2
	PHF19	NM_001286843.2		c.*134A>C		3_prime_UTR	Exon 5 of 5	NP_001273772.1	Q5T6S3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF19	ENST00000312189.10	TSL:1	c.541A>C	p.Ser181Arg	missense	Exon 5 of 5	ENSP00000310372.6	Q5T6S3-2
	PHF19	ENST00000373896.8	TSL:2 MANE Select	c.465+76A>C		intron	N/A	ENSP00000363003.3	Q5T6S3-1
	PHF19	ENST00000616568.5	TSL:1	c.522+76A>C		intron	N/A	ENSP00000483946.1	A0A087X169

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.1
DANN	Benign	0.79
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.31
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.040
Sift	Pathogenic	0.0	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-123632047;