20-35842676-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_016436.5(PHF20):c.187C>T(p.Pro63Ser) variant causes a missense change. 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: 31)
• Consequence: PHF20 NM_016436.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

Genes affected

PHF20 (HGNC:16098): (PHD finger protein 20) Predicted to enable DNA binding activity and metal ion binding activity. Involved in histone H4-K16 acetylation; histone H4-K5 acetylation; and histone H4-K8 acetylation. Located in cytosol; nuclear membrane; and nucleoplasm. Part of MLL1 complex and histone acetyltransferase 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
• PP2: Missense variant where missense usually causes diseases, PHF20
• BP4: Computational evidence support a benign effect (MetaRNN=0.37038833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF20	NM_016436.5	c.187C>T	p.Pro63Ser	missense_variant	3/18	ENST00000374012.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF20	ENST00000374012.8	c.187C>T	p.Pro63Ser	missense_variant	3/18	1	NM_016436.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Jul 17, 2023

The c.187C>T (p.P63S) alteration is located in exon 3 (coding exon 2) of the PHF20 gene. This alteration results from a C to T substitution at nucleotide position 187, causing the proline (P) at amino acid position 63 to be replaced by a serine (S). 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	0.85
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.070	T;T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.3	L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.5	N;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.12	T;D;D
Polyphen		1.0	D;.;.
Vest4		0.71
MutPred		0.36		Gain of MoRF binding (P = 0.0801);Gain of MoRF binding (P = 0.0801);Gain of MoRF binding (P = 0.0801);
MVP		0.37
MPC		1.0
ClinPred		0.84	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-34430598;