NM_015651.3:c.1002G>C

Variant names:

• chr9-120862716-C-G
• NM_015651.3:c.1002G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015651.3(PHF19):​c.1002G>C​(p.Lys334Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF19 NM_015651.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.134
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2741553).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015651.3. 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.1002G>C	p.Lys334Asn	missense	Exon 11 of 15	NP_056466.1	Q5T6S3-1
	PHF19	NM_001286840.1		c.1059G>C	p.Lys353Asn	missense	Exon 11 of 15	NP_001273769.1	A0A087X169
	PHF19	NM_001286842.1		c.375G>C	p.Lys125Asn	missense	Exon 6 of 10	NP_001273771.1	F5H8K3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF19	ENST00000373896.8	TSL:2 MANE Select	c.1002G>C	p.Lys334Asn	missense	Exon 11 of 15	ENSP00000363003.3	Q5T6S3-1
	PHF19	ENST00000616568.5	TSL:1	c.1059G>C	p.Lys353Asn	missense	Exon 11 of 15	ENSP00000483946.1	A0A087X169
	PHF19	ENST00000487555.5	TSL:1	n.425G>C		non_coding_transcript_exon	Exon 6 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.072
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-0.13
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.98	D
Vest4		0.41
MutPred		0.41		Loss of methylation at K334 (P = 8e-04)
MVP		0.13
MPC		2.0
ClinPred		0.99	D
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.40
gMVP		0.69
Mutation Taster		=54/46	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

hg19: chr9-123624994;