X-134377233-TTATC-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001015877.2(PHF6):c.-46-329_-46-326del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 112,333 control chromosomes in the GnomAD database, including 3 homozygotes. There are 198 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0066 (3 hom., 198 hem., cov: 23)
• Consequence: PHF6 NM_001015877.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.870

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-134377233-TTATC-T is Benign according to our data. Variant chrX-134377233-TTATC-T is described in ClinVar as [Likely_benign]. Clinvar id is 1212733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF6	NM_001015877.2	c.-46-329_-46-326del		intron_variant		ENST00000370803.8
PHF6	NM_032335.3	c.-46-329_-46-326del		intron_variant
PHF6	NM_032458.3	c.-46-329_-46-326del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF6	ENST00000370803.8	c.-46-329_-46-326del		intron_variant		1	NM_001015877.2	P4

Frequencies

GnomAD3 genomes AF: 0.00663 AC: 744 AN: 112279 Hom.: 3 Cov.: 23 AF XY: 0.00575 AC XY: 198 AN XY: 34433

Gnomad AFR AF: 0.00136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00216

Gnomad FIN AF: 0.00524

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00530

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00662 AC: 744 AN: 112333 Hom.: 3 Cov.: 23 AF XY: 0.00574 AC XY: 198 AN XY: 34497

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00216

Gnomad4 FIN AF: 0.00524

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00523

Alfa AF: 0.00967 Hom.: 47

Bravo AF: 0.00663

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs34685911; hg19: chrX-133511263;