dbSNP rs587780415: PHF8:p.Ser529Asn (chrX-53993641-C-T) – 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 NM_015107.3(PHF8):c.1586G>A(p.Ser529Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

PHF8
NM_015107.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0100

Publications

0 publications found

Variant links:

Genes affected

PHF8 (HGNC:20672): (PHD finger protein 8) The protein encoded by this gene is a histone lysine demethylase that preferentially acts on histones in the monomethyl or dimethyl states. The encoded protein requires Fe(2+) ion, 2-oxoglutarate, and oxygen for its catalytic activity. The protein has an N-terminal PHD finger and a central Jumonji C domain. This gene is thought to function as a transcription activator. Defects in this gene are a cause of syndromic X-linked Siderius type intellectual disability (MRXSSD) and over-expression of this gene is associated with several forms of cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

PHF8 Gene-Disease associations (from GenCC):

syndromic X-linked intellectual disability Siderius type
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

PHF8 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=0.062833905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015107.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF8	NM_015107.3	MANE Select	c.1586G>A	p.Ser529Asn	missense	Exon 13 of 22	NP_055922.1	Q9UPP1-2
PHF8	NM_001184896.1		c.1694G>A	p.Ser565Asn	missense	Exon 13 of 22	NP_001171825.1	Q9UPP1-1
PHF8	NM_001441097.1		c.1694G>A	p.Ser565Asn	missense	Exon 13 of 21	NP_001428026.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF8	ENST00000338154.11	TSL:1 MANE Select	c.1586G>A	p.Ser529Asn	missense	Exon 13 of 22	ENSP00000338868.6	Q9UPP1-2
PHF8	ENST00000357988.9	TSL:1	c.1694G>A	p.Ser565Asn	missense	Exon 13 of 22	ENSP00000350676.5	Q9UPP1-1
PHF8	ENST00000322659.12	TSL:1	c.1586G>A	p.Ser529Asn	missense	Exon 13 of 22	ENSP00000319473.8	Q9UPP1-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.6

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.023

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.46

M_CAP

Benign

0.0062

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

PhyloP100

-0.010

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.55

REVEL

Benign

0.031

Sift

Benign

0.61

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.044

MutPred

0.38

Loss of disorder (P = 0.1098)

MVP

0.27

MPC

0.47

ClinPred

0.024

GERP RS

-5.2

Varity_R

0.055

gMVP

0.29

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over