13-49496054-C-G

Variant names:

• chr13-49496054-C-G
• rs947012356
• NM_001040443.3:c.53C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040443.3(PHF11):​c.53C>G​(p.Pro18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,437,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: PHF11 NM_001040443.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 1 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]

SETDB2-PHF11 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057760686).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040443.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF11	NM_001040443.3	MANE Select	c.53C>G	p.Pro18Arg	missense	Exon 1 of 10	NP_001035533.1	Q9UIL8-1
	PHF11	NM_001040444.3		c.-227C>G		5_prime_UTR	Exon 1 of 11	NP_001035534.1	Q9UIL8-2
	PHF11	NM_001419873.1		c.-580C>G		5_prime_UTR	Exon 1 of 11	NP_001406802.1	Q9UIL8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF11	ENST00000378319.8	TSL:1 MANE Select	c.53C>G	p.Pro18Arg	missense	Exon 1 of 10	ENSP00000367570.3	Q9UIL8-1
	PHF11	ENST00000941732.1		c.53C>G	p.Pro18Arg	missense	Exon 1 of 10	ENSP00000611791.1
	PHF11	ENST00000873990.1		c.53C>G	p.Pro18Arg	missense	Exon 1 of 10	ENSP00000544049.1

Frequencies

GnomAD3 genomes AF: 0.00000665 AC: 1 AN: 150356 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000216

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1287154 Hom.: 0 Cov.: 31 AF XY: 0.00000315 AC XY: 2 AN XY: 634242

African (AFR) AF: 0.00 AC: 0 AN: 25302

American (AMR) AF: 0.00 AC: 0 AN: 24286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21460

East Asian (EAS) AF: 0.00 AC: 0 AN: 26760

South Asian (SAS) AF: 0.0000279 AC: 2 AN: 71580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4444

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029820

Other (OTH) AF: 0.00 AC: 0 AN: 52476

GnomAD4 genome AF: 0.00000665 AC: 1 AN: 150356 Hom.: 0 Cov.: 33 AF XY: 0.0000136 AC XY: 1 AN XY: 73434

African (AFR) AF: 0.00 AC: 0 AN: 40998

American (AMR) AF: 0.00 AC: 0 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5028

South Asian (SAS) AF: 0.000216 AC: 1 AN: 4632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67488

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.9
DANN	Benign	0.70
DEOGEN2	Benign	0.081	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.050
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.060
Sift	Benign	0.14	T
Sift4G	Benign	0.10	T
Polyphen		0.23	B
Vest4		0.026
MutPred		0.30		Gain of MoRF binding (P = 0.0052)
MVP		0.18
MPC		0.31
ClinPred		0.082	T
GERP RS		1.2
PromoterAI		-0.029	Neutral
Varity_R		0.024
gMVP		0.31
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs947012356; hg19: chr13-50070190;