chr9-120858047-C-T

Position:

• chr9-120858047-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015651.3(PHF19):​c.1640G>A​(p.Gly547Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.01

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF19	NM_015651.3	c.1640G>A	p.Gly547Glu	missense_variant	15/15	ENST00000373896.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF19	ENST00000373896.8	c.1640G>A	p.Gly547Glu	missense_variant	15/15	2	NM_015651.3	P1
PHF19	ENST00000616568.5	c.1697G>A	p.Gly566Glu	missense_variant	15/15	1
PHF19	ENST00000487555.5	n.975G>A		non_coding_transcript_exon_variant	9/9	1
PHF19	ENST00000419155.5	c.1013G>A	p.Gly338Glu	missense_variant	10/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2023

The c.1640G>A (p.G547E) alteration is located in exon 15 (coding exon 14) of the PHF19 gene. This alteration results from a G to A substitution at nucleotide position 1640, causing the glycine (G) at amino acid position 547 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T;.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.3	.;.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.5	D;.;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;.;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.79
MutPred		0.64		.;.;Loss of methylation at R548 (P = 0.0422);
MVP		0.43
MPC		2.3
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.80

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: rs2045398598; hg19: chr9-123620325;