chrX-134377648-C-G

Variant names:

• chrX-134377648-C-G
• rs2077283804
• NM_001015877.2:c.31C>G

Variant summary

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

The NM_001015877.2(PHF6):​c.31C>G​(p.Pro11Ala) 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. 15/20 in silico tools predict 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: 22)
• Consequence: PHF6 NM_001015877.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

Genes affected

PHF6 (HGNC:18145): (PHD finger protein 6) This gene is a member of the plant homeodomain (PHD)-like finger (PHF) family. It encodes a protein with two PHD-type zinc finger domains, indicating a potential role in transcriptional regulation, that localizes to the nucleolus. Mutations affecting the coding region of this gene or the splicing of the transcript have been associated with Borjeson-Forssman-Lehmann syndrome (BFLS), a disorder characterized by cognitive disability, epilepsy, hypogonadism, hypometabolism, obesity, swelling of subcutaneous tissue of the face, narrow palpebral fissures, and large ears. Alternate splicing results in multiple transcript variants, encoding different isoforms. [provided by RefSeq, Jun 2010]

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=0.074515134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF6	NM_001015877.2	c.31C>G	p.Pro11Ala	missense_variant	Exon 2 of 11	ENST00000370803.8	NP_001015877.1
PHF6	NM_032458.3	c.31C>G	p.Pro11Ala	missense_variant	Exon 2 of 10		NP_115834.1
PHF6	NM_032335.3	c.31C>G	p.Pro11Ala	missense_variant	Exon 2 of 8		NP_115711.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF6	ENST00000370803.8	c.31C>G	p.Pro11Ala	missense_variant	Exon 2 of 11	1	NM_001015877.2	ENSP00000359839.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.094	T;T;T;.;.
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.80	.;T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.075	T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	-0.34	N;N;.;.;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.50	N;N;.;N;N
REVEL	Benign	0.18
Sift	Benign	0.49	T;T;.;T;T
Sift4G	Benign	0.63	T;T;T;T;T
Polyphen		0.0	B;B;.;.;B
Vest4		0.11
MutPred		0.21		Loss of glycosylation at P11 (P = 0.0156);Loss of glycosylation at P11 (P = 0.0156);Loss of glycosylation at P11 (P = 0.0156);Loss of glycosylation at P11 (P = 0.0156);Loss of glycosylation at P11 (P = 0.0156);
MVP		0.62
MPC		1.0
ClinPred		0.073	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2077283804; hg19: chrX-133511678;