chr13-49518114-G-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001040443.3(PHF11):c.421G>A(p.Ala141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,607,722 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
PHF11
NM_001040443.3 missense
NM_001040443.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 2.25
Publications
2 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152104
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000401 AC: 1AN: 249576 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
249576
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1455618Hom.: 0 Cov.: 27 AF XY: 0.00000276 AC XY: 2AN XY: 724490 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1455618
Hom.:
Cov.:
27
AF XY:
AC XY:
2
AN XY:
724490
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33296
American (AMR)
AF:
AC:
0
AN:
44408
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26060
East Asian (EAS)
AF:
AC:
0
AN:
39582
South Asian (SAS)
AF:
AC:
1
AN:
85726
European-Finnish (FIN)
AF:
AC:
0
AN:
53364
Middle Eastern (MID)
AF:
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1107270
Other (OTH)
AF:
AC:
0
AN:
60160
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74310 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152104
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74310
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41400
American (AMR)
AF:
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5200
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
1
AN:
10594
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68020
Other (OTH)
AF:
AC:
0
AN:
2094
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ExAC
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Dec 04, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.421G>A (p.A141T) alteration is located in exon 4 (coding exon 4) of the PHF11 gene. This alteration results from a G to A substitution at nucleotide position 421, causing the alanine (A) at amino acid position 141 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;.;T;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;.
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;.;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;D;.;.;.;.
Vest4
MutPred
Loss of ubiquitination at K137 (P = 0.063);Loss of ubiquitination at K137 (P = 0.063);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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