rs7065696

chrX-53947621-C-GchrX-53947621-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015107.3(PHF8):c.2540-3378G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 111,576 control chromosomes in the GnomAD database, including 1,214 homozygotes. There are 4,321 hemizygotes in GnomAD. 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: 𝑓 0.14 (1214 hom., 4321 hem., cov: 23)
• Consequence: PHF8 NM_015107.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

Genes affected

PHF8 (HGNC:20672): (PHD finger protein 8) The protein encoded by this gene is a histone lysine demethylase that preferentially acts on histones in the monomethyl or dimethyl states. The encoded protein requires Fe(2+) ion, 2-oxoglutarate, and oxygen for its catalytic activity. The protein has an N-terminal PHD finger and a central Jumonji C domain. This gene is thought to function as a transcription activator. Defects in this gene are a cause of syndromic X-linked Siderius type intellectual disability (MRXSSD) and over-expression of this gene is associated with several forms of cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF8	NM_015107.3	c.2540-3378G>C		intron_variant		ENST00000338154.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF8	ENST00000338154.11	c.2540-3378G>C		intron_variant		1	NM_015107.3	P2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 15693 AN: 111522 Hom.: 1215 Cov.: 23 AF XY: 0.128 AC XY: 4302 AN XY: 33720

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.0443

Gnomad EAS AF: 0.000835

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.0971

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.0968

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.141 AC: 15710 AN: 111576 Hom.: 1214 Cov.: 23 AF XY: 0.128 AC XY: 4321 AN XY: 33784

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.0679

Gnomad4 ASJ AF: 0.0443

Gnomad4 EAS AF: 0.000837

Gnomad4 SAS AF: 0.0475

Gnomad4 FIN AF: 0.0971

Gnomad4 NFE AF: 0.0968

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0827 Hom.: 1677

Bravo AF: 0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.3
Dann	Benign	0.58

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: rs7065696; hg19: chrX-53974054;