Genetic Variant PHF11:p.Val12Glu (chr13-49496036-T-A) – 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_001040443.3(PHF11):c.35T>A(p.Val12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,469,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PHF11
NM_001040443.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.12

Publications

1 publications found

Variant links:

Genes affected

PHF11 (HGNC:17024): (PHD finger protein 11) This gene encodes a protein containing a PHD (plant homeodomain) type zinc finger. This gene has been identified in some studies as a candidate gene for asthma. Naturally-occurring readthrough transcription may occur from the upstream SETDB2 (SET domain bifurcated 2) gene to this locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

PHF11 links:

SETDB2-PHF11 (HGNC:):

SETDB2-PHF11 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=0.07310495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF11	NM_001040443.3 link	c.35T>A	p.Val12Glu	missense_variant	Exon 1 of 10	ENST00000378319.8	NP_001035533.1	Q9UIL8-1B4DDL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8 link	c.35T>A	p.Val12Glu	missense_variant	Exon 1 of 10	1	NM_001040443.3	ENSP00000367570.3		Q9UIL8-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000228

AC:

AN:

1318448

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

650160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26490

American (AMR)

AF:

0.00

AC:

AN:

26346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23010

East Asian (EAS)

AF:

0.00

AC:

AN:

28152

South Asian (SAS)

AF:

0.00

AC:

AN:

73468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5060

European-Non Finnish (NFE)

AF:

0.0000286

AC:

AN:

1048846

Other (OTH)

AF:

0.00

AC:

AN:

54576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41170

American (AMR)

AF:

0.0000657

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67744

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.35T>A (p.V12E) alteration is located in exon 1 (coding exon 1) of the PHF11 gene. This alteration results from a T to A substitution at nucleotide position 35, causing the valine (V) at amino acid position 12 to be replaced by a glutamic acid (E). 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

Benign

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.36

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.091

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.26

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

PhyloP100

-1.1

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.38

N;.

REVEL

Benign

0.13

Sift

Uncertain

0.017

D;.

Sift4G

Uncertain

0.041

D;D

Polyphen

0.0

B;B

Vest4

0.13

MutPred

0.21

Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);

MVP

0.25

MPC

0.41

ClinPred

0.13

GERP RS

-2.0

PromoterAI

0.072

Neutral

(source)

Varity_R

0.082

gMVP

0.22

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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13-49496036-T-A

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