rs148215758

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_015107.3(PHF8):c.441T>G(p.Val147Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,206,266 control chromosomes in the GnomAD database, including 446 homozygotes. There are 11,694 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 34 hom., 727 hem., cov: 23)

Exomes 𝑓: 0.031 ( 412 hom. 10967 hem. )

Consequence

PHF8
NM_015107.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00800

Publications

4 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, Labcorp Genetics (formerly Invitae), G2P

PHF8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.067).

BP6

Variant X-54017674-A-C is Benign according to our data. Variant chrX-54017674-A-C is described in ClinVar as Benign. ClinVar VariationId is 129890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.008 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0229 (2556/111843) while in subpopulation NFE AF = 0.034 (1805/53145). AF 95% confidence interval is 0.0327. There are 34 homozygotes in GnomAd4. There are 727 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 34 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF8	NM_015107.3 link	c.441T>G	p.Val147Val	synonymous_variant	Exon 5 of 22	ENST00000338154.11	NP_055922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF8	ENST00000338154.11 link	c.441T>G	p.Val147Val	synonymous_variant	Exon 5 of 22	1	NM_015107.3	ENSP00000338868.6

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

2560

AN:

111789

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00468

Gnomad AMI

AF:

0.0294

Gnomad AMR

AF:

0.0199

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0100

Gnomad FIN

AF:

0.0448

Gnomad MID

AF:

0.0464

Gnomad NFE

AF:

0.0340

Gnomad OTH

AF:

0.0245

GnomAD2 exomes

AF:

0.0259

AC:

4745

AN:

183004

AF XY:

0.0255

show subpopulations

Gnomad AFR exome

AF:

0.00365

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.0201

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0514

Gnomad NFE exome

AF:

0.0373

Gnomad OTH exome

AF:

0.0281

GnomAD4 exome

AF:

0.0311

AC:

34036

AN:

1094423

Hom.:

412

Cov.:

AF XY:

0.0305

AC XY:

10967

AN XY:

360047

show subpopulations

African (AFR)

AF:

0.00330

AC:

AN:

26348

American (AMR)

AF:

0.0126

AC:

443

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.0200

AC:

387

AN:

19366

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30198

South Asian (SAS)

AF:

0.0118

AC:

640

AN:

54029

European-Finnish (FIN)

AF:

0.0492

AC:

1996

AN:

40531

Middle Eastern (MID)

AF:

0.0352

AC:

145

AN:

4124

European-Non Finnish (NFE)

AF:

0.0347

AC:

29129

AN:

838680

Other (OTH)

AF:

0.0263

AC:

1208

AN:

45949

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1034

2067

3101

4134

5168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1100

2200

3300

4400

5500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0229

AC:

2556

AN:

111843

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

727

AN XY:

34009

show subpopulations

African (AFR)

AF:

0.00464

AC:

143

AN:

30810

American (AMR)

AF:

0.0199

AC:

210

AN:

10551

Ashkenazi Jewish (ASJ)

AF:

0.0136

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3549

South Asian (SAS)

AF:

0.00970

AC:

AN:

2680

European-Finnish (FIN)

AF:

0.0448

AC:

270

AN:

6028

Middle Eastern (MID)

AF:

0.0463

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0340

AC:

1805

AN:

53145

Other (OTH)

AF:

0.0235

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

104

209

313

418

522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0259

Hom.:

377

Bravo

AF:

0.0201

EpiCase

AF:

0.0379

EpiControl

AF:

0.0351

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 05, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 07, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.8

(source)

DANN

Benign

0.87

PhyloP100

-0.0080

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over