rs930144261

Variant names:

• chr13-49520935-A-C
• rs930144261
• NM_001040443.3:c.500A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040443.3(PHF11):​c.500A>C​(p.Gln167Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,582,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: PHF11 NM_001040443.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17663088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF11	NM_001040443.3	c.500A>C	p.Gln167Pro	missense_variant	Exon 5 of 10	ENST00000378319.8	NP_001035533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8	c.500A>C	p.Gln167Pro	missense_variant	Exon 5 of 10	1	NM_001040443.3	ENSP00000367570.3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152246 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000350 AC: 5 AN: 1430572 Hom.: 0 Cov.: 23 AF XY: 0.00000281 AC XY: 2 AN XY: 712344

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000275

Gnomad4 OTH exome AF: 0.0000338

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152364 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74510

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.500A>C (p.Q167P) alteration is located in exon 5 (coding exon 5) of the PHF11 gene. This alteration results from a A to C substitution at nucleotide position 500, causing the glutamine (Q) at amino acid position 167 to be replaced by a proline (P). 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	0.061
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T;T;.;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.49	T;T;.;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.4	L;.;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.010	D;D;D;D;D
Sift4G	Uncertain	0.053	T;D;T;T;T
Polyphen		0.95	P;.;.;.;.
Vest4		0.34
MutPred		0.41		Gain of glycosylation at Q167 (P = 0.0599);.;.;.;.;
MVP		0.74
MPC		0.64
ClinPred		0.63	D
GERP RS		-0.45
Varity_R		0.21
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs930144261; hg19: chr13-50095071;