chr13-49513117-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).

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.275G>C	p.Ser92Thr	missense	Exon 3 of 10	NP_001035533.1	Q9UIL8-1
	SETDB2-PHF11	NM_001320727.2		c.1757G>C	p.Ser586Thr	missense	Exon 13 of 20	NP_001307656.1
	PHF11	NM_001040444.3		c.158G>C	p.Ser53Thr	missense	Exon 4 of 11	NP_001035534.1	Q9UIL8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF11	ENST00000378319.8	TSL:1 MANE Select	c.275G>C	p.Ser92Thr	missense	Exon 3 of 10	ENSP00000367570.3	Q9UIL8-1
	PHF11	ENST00000488958.5	TSL:1	c.158G>C	p.Ser53Thr	missense	Exon 3 of 10	ENSP00000417539.1	Q9UIL8-2
	PHF11	ENST00000465045.5	TSL:1	n.158G>C		non_coding_transcript_exon	Exon 4 of 12	ENSP00000418630.1	J3KR57

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 v4.9

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
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.47
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.076
Sift	Benign	0.044	D
Sift4G	Benign	0.11	T
Polyphen		0.28	B
Vest4		0.14
MutPred		0.40		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;