Genetic Variant PHF14:p.Gly267Cys (chr7-10983058-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001007157.2(PHF14):c.799G>T(p.Gly267Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000814 in 1,597,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

PHF14
NM_001007157.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

Publications

0 publications found

Variant links:

Genes affected

PHF14 (HGNC:22203): (PHD finger protein 14) Predicted to enable histone binding activity. Predicted to be involved in histone H3-K14 acetylation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including lung alveolus development; negative regulation of mesenchymal cell proliferation involved in lung development; and negative regulation of platelet-derived growth factor receptor-alpha signaling pathway. Predicted to be located in nucleus. Predicted to be part of MOZ/MORF histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

PHF14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1923168).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007157.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF14	NM_001007157.2	MANE Select	c.799G>T	p.Gly267Cys	missense	Exon 3 of 18	NP_001007158.1	O94880-3
PHF14	NM_014660.4		c.799G>T	p.Gly267Cys	missense	Exon 3 of 17	NP_055475.2
PHF14	NR_033435.2		n.565-7645G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF14	ENST00000634607.2	TSL:5 MANE Select	c.799G>T	p.Gly267Cys	missense	Exon 3 of 18	ENSP00000489535.1	O94880-3
PHF14	ENST00000403050.7	TSL:1	c.799G>T	p.Gly267Cys	missense	Exon 3 of 17	ENSP00000385795.3	O94880-1
PHF14	ENST00000931753.1		c.799G>T	p.Gly267Cys	missense	Exon 4 of 19	ENSP00000601812.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000870

AC:

AN:

229830

AF XY:

0.0000160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000761

AC:

AN:

1445306

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718780

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.0000454

AC:

AN:

44088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26010

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

85448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40864

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000811

AC:

AN:

1109856

Other (OTH)

AF:

0.00

AC:

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0072

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

5.2

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.12

Sift

Uncertain

0.0020

Polyphen

0.95

Vest4

0.27

MutPred

0.41

Loss of MoRF binding (P = 0.079)

MVP

0.59

MPC

0.12

ClinPred

0.80

GERP RS

4.0

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.6

Varity_R

0.37

gMVP

0.093

Mutation Taster

=98/2

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over