rs77581173

Variant names:

• chrX-54014554-G-A
• rs77581173
• NM_015107.3:c.606C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-54014554-G-A
• chrX-54014554-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015107.3(PHF8):​c.606C>T​(p.Asn202Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,198,351 control chromosomes in the GnomAD database, including 50 homozygotes. There are 779 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (4 hom., 112 hem., cov: 22)
  • Exomes 𝑓: 0.0019 (46 hom. 667 hem.)
• Consequence: PHF8 NM_015107.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.00200

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant X-54014554-G-A is Benign according to our data. Variant chrX-54014554-G-A is described in ClinVar as [Benign]. Clinvar id is 129888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.002 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF8	NM_015107.3	c.606C>T	p.Asn202Asn	synonymous_variant	Exon 7 of 22	ENST00000338154.11	NP_055922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF8	ENST00000338154.11	c.606C>T	p.Asn202Asn	synonymous_variant	Exon 7 of 22	1	NM_015107.3	ENSP00000338868.6

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 300 AN: 111767 Hom.: 4 Cov.: 22 AF XY: 0.00324 AC XY: 110 AN XY: 33947

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000573

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0687

Gnomad SAS AF: 0.00369

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00600

GnomAD3 exomes AF: 0.00605 AC: 1094 AN: 180762 Hom.: 28 AF XY: 0.00554 AC XY: 362 AN XY: 65300

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0745

Gnomad SAS exome AF: 0.00167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00379

GnomAD4 exome AF: 0.00192 AC: 2089 AN: 1086530 Hom.: 46 Cov.: 28 AF XY: 0.00189 AC XY: 667 AN XY: 352422

Gnomad4 AFR exome AF: 0.000610

Gnomad4 AMR exome AF: 0.0000569

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0568

Gnomad4 SAS exome AF: 0.00188

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00521

GnomAD4 genome AF: 0.00269 AC: 301 AN: 111821 Hom.: 4 Cov.: 22 AF XY: 0.00329 AC XY: 112 AN XY: 34011

Gnomad4 AFR AF: 0.00104

Gnomad4 AMR AF: 0.000573

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.00370

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00592

Alfa AF: 0.00132 Hom.: 10

Bravo AF: 0.00332

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jun 12, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

May 06, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.4
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs77581173; hg19: chrX-54040987; COSMIC: COSV57678176; COSMIC: COSV57678176;