dbSNP rs34685911: PHF6:c.-46-329_-46-326delATCT (chrX-134377233-TTATC-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001015877.2(PHF6):c.-46-329_-46-326delATCT 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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.870

Publications

0 publications found

Variant links:

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]

PHF6 Gene-Disease associations (from GenCC):

Borjeson-Forssman-Lehmann syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Illumina, G2P, Orphanet

PHF6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 1212733.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015877.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHF6	NM_001015877.2	MANE Select	c.-46-329_-46-326delATCT	intron	N/A	NP_001015877.1	Q8IWS0-1
PHF6	NM_032458.3		c.-46-329_-46-326delATCT	intron	N/A	NP_115834.1	Q8IWS0-1
PHF6	NM_032335.3		c.-46-329_-46-326delATCT	intron	N/A	NP_115711.2	Q8IWS0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHF6	ENST00000370803.8	TSL:1 MANE Select	c.-46-338_-46-335delTATC	intron	N/A	ENSP00000359839.4	Q8IWS0-1
PHF6	ENST00000332070.7	TSL:1	c.-46-338_-46-335delTATC	intron	N/A	ENSP00000329097.3	Q8IWS0-1
PHF6	ENST00000370799.5	TSL:1	c.-46-338_-46-335delTATC	intron	N/A	ENSP00000359835.1	Q5JRC6

Frequencies

GnomAD3 genomes

AF:

0.00663

AC:

744

AN:

112279

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00574

AC XY:

198

AN XY:

34497

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

31049

American (AMR)

AF:

0.0112

AC:

118

AN:

10563

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3622

South Asian (SAS)

AF:

0.00216

AC:

AN:

2774

European-Finnish (FIN)

AF:

0.00524

AC:

AN:

6112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0101

AC:

538

AN:

53141

Other (OTH)

AF:

0.00523

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00967

Hom.:

Bravo

AF:

0.00663

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.87

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over