13-49506663-A-G

Variant names:

• chr13-49506663-A-G
• rs773818777
• NM_001040443.3:c.123A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001040443.3(PHF11):​c.123A>G​(p.Glu41Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHF11 NM_001040443.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.256 with no splicing effect.

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.123A>G	p.Glu41Glu	synonymous	Exon 2 of 10	NP_001035533.1	Q9UIL8-1
	SETDB2-PHF11	NM_001320727.2		c.1605A>G	p.Glu535Glu	synonymous	Exon 12 of 20	NP_001307656.1
	PHF11	NM_001040444.3		c.6A>G	p.Glu2Glu	synonymous	Exon 3 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.123A>G	p.Glu41Glu	synonymous	Exon 2 of 10	ENSP00000367570.3	Q9UIL8-1
	PHF11	ENST00000488958.5	TSL:1	c.6A>G	p.Glu2Glu	synonymous	Exon 2 of 10	ENSP00000417539.1	Q9UIL8-2
	PHF11	ENST00000465045.5	TSL:1	n.6A>G		non_coding_transcript_exon	Exon 3 of 12	ENSP00000418630.1	J3KR57

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460806 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726806

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111144

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.9
DANN	Benign	0.61
PhyloP100		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs773818777; hg19: chr13-50080799;