Variant 13-49506663-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040443.3(PHF11):c.123A>T(p.Glu41Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PHF11
NM_001040443.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.256

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13933805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF11	NM_001040443.3 linkuse as main transcript	c.123A>T	p.Glu41Asp	missense_variant	2/10	ENST00000378319.8
SETDB2-PHF11	NR_135324.2 linkuse as main transcript	n.2663-6396A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF11	ENST00000378319.8 linkuse as main transcript	c.123A>T	p.Glu41Asp	missense_variant	2/10	1	NM_001040443.3	P2	Q9UIL8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251242

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460806

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000576

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.123A>T (p.E41D) alteration is located in exon 2 (coding exon 2) of the PHF11 gene. This alteration results from a A to T substitution at nucleotide position 123, causing the glutamic acid (E) at amino acid position 41 to be replaced by an aspartic acid (D). 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

0.66

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;.;T;T;.

Eigen

Benign

-0.076

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

T;T;.;T;T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.3

M;.;.;.;.;.

MutationTaster

Benign

0.87

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

N;.;N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.21

T;.;T;T;D;T

Sift4G

Benign

0.27

T;T;T;T;T;T

Polyphen

0.95

P;P;.;.;.;.

Vest4

0.18

MutPred

0.38

Loss of methylation at K42 (P = 0.0677);Loss of methylation at K42 (P = 0.0677);.;.;.;.;

MVP

0.80

MPC

0.54

ClinPred

0.17

GERP RS

2.3

Varity_R

0.070

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over