Genetic Variant ENST00000312189.10:c.543T>G (chr9-120869767-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.15

Publications

46 publications found

Variant links:

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]

PHF19 links:

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ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF19	NM_015651.3 link	c.465+78T>G		intron_variant	Intron 5 of 14	ENST00000373896.8	NP_056466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PHF19	ENST00000312189.10 link	c.543T>G	p.Ser181Arg	missense_variant	Exon 5 of 5	1		ENSP00000310372.6
PHF19	ENST00000373896.8 link	c.465+78T>G		intron_variant	Intron 5 of 14	2	NM_015651.3	ENSP00000363003.3
PHF19	ENST00000616568.5 link	c.522+78T>G		intron_variant	Intron 5 of 14	1		ENSP00000483946.1
PHF19	ENST00000436309.5 link	c.465+78T>G		intron_variant	Intron 5 of 5	4		ENSP00000408479.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1448590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718996

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.00

AC:

AN:

42802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25782

East Asian (EAS)

AF:

0.00

AC:

AN:

39312

South Asian (SAS)

AF:

0.00

AC:

AN:

83594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105728

Other (OTH)

AF:

0.00

AC:

AN:

59920

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

55430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.22

(source)

DANN

Benign

0.81

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.26

M_CAP

Benign

0.0021

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

PhyloP100

-2.1

PROVEAN

Benign

-0.80

REVEL

Benign

0.052

Sift

Pathogenic

0.0

Polyphen

0.0

Vest4

0.14

MutPred

0.15

Loss of ubiquitination at K185 (P = 0.0184);

MVP

0.043

ClinPred

0.087

GERP RS

-3.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over