13-49513117-G-C

Variant names:

• chr13-49513117-G-C
• rs747635592
• NM_001040443.3:c.275G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040443.3(PHF11):​c.275G>C​(p.Ser92Thr) 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. 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. S92N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF11 NM_001040443.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16074973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF11	NM_001040443.3	c.275G>C	p.Ser92Thr	missense_variant	Exon 3 of 10	ENST00000378319.8	NP_001035533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8	c.275G>C	p.Ser92Thr	missense_variant	Exon 3 of 10	1	NM_001040443.3	ENSP00000367570.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.76
DEOGEN2	Benign	0.12	T;.;T;.;T;T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.72	T;T;T;.;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L;.;.;.;.;.;.
PhyloP100		0.47
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N;.;N;N;N;N;N
REVEL	Benign	0.076
Sift	Benign	0.044	D;.;T;T;D;T;T
Sift4G	Benign	0.11	T;T;T;T;T;T;T
Polyphen		0.28	B;B;.;.;.;.;.
Vest4		0.14
MutPred		0.40		Loss of disorder (P = 0.0632);Loss of disorder (P = 0.0632);.;.;.;.;.;
MVP		0.51
MPC		0.38
ClinPred		0.14	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.55
Mutation Taster		=96/4	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: rs747635592; hg19: chr13-50087253;