rs148215758

Variant names:

• chrX-54017674-A-C
• rs148215758
• NM_015107.3:c.441T>G

Your query was ambiguous. Multiple possible variants found:

• chrX-54017674-A-C
• chrX-54017674-A-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_015107.3(PHF8):​c.441T>G​(p.Val147Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,206,266 control chromosomes in the GnomAD database, including 446 homozygotes. There are 11,694 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (34 hom., 727 hem., cov: 23)
  • Exomes 𝑓: 0.031 (412 hom. 10967 hem.)
• Consequence: PHF8 NM_015107.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00800
• Publications: 4 publications found

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]

PHF8 Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability Siderius type

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.067).
• BP6: Variant X-54017674-A-C is Benign according to our data. Variant chrX-54017674-A-C is described in ClinVar as Benign. ClinVar VariationId is 129890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.008 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0229 (2556/111843) while in subpopulation NFE AF = 0.034 (1805/53145). AF 95% confidence interval is 0.0327. There are 34 homozygotes in GnomAd4. There are 727 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015107.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF8	NM_015107.3	MANE Select	c.441T>G	p.Val147Val	synonymous	Exon 5 of 22	NP_055922.1	Q9UPP1-2
	PHF8	NM_001184896.1		c.549T>G	p.Val183Val	synonymous	Exon 5 of 22	NP_001171825.1	Q9UPP1-1
	PHF8	NM_001441096.1		c.549T>G	p.Val183Val	synonymous	Exon 5 of 22	NP_001428025.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF8	ENST00000338154.11	TSL:1 MANE Select	c.441T>G	p.Val147Val	synonymous	Exon 5 of 22	ENSP00000338868.6	Q9UPP1-2
	PHF8	ENST00000357988.9	TSL:1	c.549T>G	p.Val183Val	synonymous	Exon 5 of 22	ENSP00000350676.5	Q9UPP1-1
	PHF8	ENST00000322659.12	TSL:1	c.441T>G	p.Val147Val	synonymous	Exon 5 of 22	ENSP00000319473.8	Q9UPP1-5

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 2560 AN: 111789 Hom.: 34 Cov.: 23

Gnomad AFR AF: 0.00468

Gnomad AMI AF: 0.0294

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0100

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0464

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.0245

GnomAD2 exomes AF: 0.0259 AC: 4745 AN: 183004 AF XY: 0.0255

Gnomad AFR exome AF: 0.00365

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0514

Gnomad NFE exome AF: 0.0373

Gnomad OTH exome AF: 0.0281

GnomAD4 exome AF: 0.0311 AC: 34036 AN: 1094423 Hom.: 412 Cov.: 29 AF XY: 0.0305 AC XY: 10967 AN XY: 360047

African (AFR) AF: 0.00330 AC: 87 AN: 26348

American (AMR) AF: 0.0126 AC: 443 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.0200 AC: 387 AN: 19366

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30198

South Asian (SAS) AF: 0.0118 AC: 640 AN: 54029

European-Finnish (FIN) AF: 0.0492 AC: 1996 AN: 40531

Middle Eastern (MID) AF: 0.0352 AC: 145 AN: 4124

European-Non Finnish (NFE) AF: 0.0347 AC: 29129 AN: 838680

Other (OTH) AF: 0.0263 AC: 1208 AN: 45949

GnomAD4 genome AF: 0.0229 AC: 2556 AN: 111843 Hom.: 34 Cov.: 23 AF XY: 0.0214 AC XY: 727 AN XY: 34009

African (AFR) AF: 0.00464 AC: 143 AN: 30810

American (AMR) AF: 0.0199 AC: 210 AN: 10551

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 36 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3549

South Asian (SAS) AF: 0.00970 AC: 26 AN: 2680

European-Finnish (FIN) AF: 0.0448 AC: 270 AN: 6028

Middle Eastern (MID) AF: 0.0463 AC: 10 AN: 216

European-Non Finnish (NFE) AF: 0.0340 AC: 1805 AN: 53145

Other (OTH) AF: 0.0235 AC: 36 AN: 1532

Alfa AF: 0.0259 Hom.: 377

Bravo AF: 0.0201

EpiCase AF: 0.0379

EpiControl AF: 0.0351

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.8
DANN	Benign	0.87
PhyloP100		-0.0080
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs148215758; hg19: chrX-54044107;