13-49513139-G-T

Position:

• chr13-49513139-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040443.3(PHF11):​c.297G>T​(p.Lys99Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF11 NM_001040443.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.309

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]

SETDB2-PHF11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36934897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF11	NM_001040443.3	c.297G>T	p.Lys99Asn	missense_variant	3/10	ENST00000378319.8	NP_001035533.1
SETDB2-PHF11	NR_135324.2	n.2743G>T		non_coding_transcript_exon_variant	13/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8	c.297G>T	p.Lys99Asn	missense_variant	3/10	1	NM_001040443.3	ENSP00000367570	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.297G>T (p.K99N) alteration is located in exon 3 (coding exon 3) of the PHF11 gene. This alteration results from a G to T substitution at nucleotide position 297, causing the lysine (K) at amino acid position 99 to be replaced by an asparagine (N). 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	0.96
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;.;T;.;T;T;.
Eigen	Benign	0.024
Eigen_PC	Benign	-0.013
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.70	T;T;T;.;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.37	T;T;T;T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.7	M;.;.;.;.;.;.
MutationTaster	Benign	0.58	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.4	D;.;D;D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.041	D;.;D;D;T;D;D
Sift4G	Uncertain	0.033	D;T;T;D;T;T;D
Polyphen		1.0	D;D;.;.;.;.;.
Vest4		0.27
MutPred		0.35		Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);.;.;.;.;.;
MVP		0.82
MPC		0.71
ClinPred		0.89	D
GERP RS		0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-50087275;