Variant chrX-134377688-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001015877.2(PHF6):c.71G>C(p.Arg24Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000273 in 1,097,047 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

PHF6
NM_001015877.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.01

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a region_of_interest Extended PHD1 domain (ePHD1) (size 118) in uniprot entity PHF6_HUMAN there are 5 pathogenic changes around while only 1 benign (83%) in NM_001015877.2

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23678541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PHF6	NM_001015877.2 linkuse as main transcript	c.71G>C	p.Arg24Thr	missense_variant	2/11	ENST00000370803.8
PHF6	NM_032458.3 linkuse as main transcript	c.71G>C	p.Arg24Thr	missense_variant	2/10
PHF6	NM_032335.3 linkuse as main transcript	c.71G>C	p.Arg24Thr	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF6	ENST00000370803.8 linkuse as main transcript	c.71G>C	p.Arg24Thr	missense_variant	2/11	1	NM_001015877.2	P4	Q8IWS0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183426

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097047

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362439

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000357

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.71G>C (p.R24T) alteration is located in exon 2 (coding exon 1) of the PHF6 gene. This alteration results from a G to C substitution at nucleotide position 71, causing the arginine (R) at amino acid position 24 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

T;T;T;.;.

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.082

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Uncertain

-0.087

MutationAssessor

Benign

0.97

L;L;.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.4

N;N;.;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.077

T;T;.;T;T

Sift4G

Uncertain

0.028

D;D;D;D;D

Polyphen

0.22

B;B;.;.;P

Vest4

0.43

MutPred

0.33

Loss of stability (P = 0.0184);Loss of stability (P = 0.0184);Loss of stability (P = 0.0184);Loss of stability (P = 0.0184);Loss of stability (P = 0.0184);

MVP

0.88

MPC

1.6

ClinPred

0.61

GERP RS

5.8

Varity_R

0.39

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over