rs222852

Variant names:

• chr17-7237287-A-G
• rs222852
• NM_024297.3:c.159+98T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-7237287-A-G
• chr17-7237287-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024297.3(PHF23):​c.159+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,061,798 control chromosomes in the GnomAD database, including 106,332 homozygotes. 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 0.48 (18118 hom., cov: 31)
  • Exomes 𝑓: 0.43 (88214 hom.)
• Consequence: PHF23 NM_024297.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 36 publications found

Genes affected

PHF23 (HGNC:28428): (PHD finger protein 23) Predicted to enable metal ion binding activity. Involved in negative regulation of autophagosome assembly; negative regulation of autophagosome maturation; and positive regulation of protein ubiquitination. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF23	NM_024297.3	c.159+98T>C		intron_variant	Intron 3 of 4	ENST00000320316.8	NP_077273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF23	ENST00000320316.8	c.159+98T>C		intron_variant	Intron 3 of 4	1	NM_024297.3	ENSP00000322579.3

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72878 AN: 151750 Hom.: 18107 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.433 AC: 394259 AN: 909930 Hom.: 88214 AF XY: 0.429 AC XY: 199210 AN XY: 464410

African (AFR) AF: 0.618 AC: 13114 AN: 21224

American (AMR) AF: 0.516 AC: 15582 AN: 30202

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 7698 AN: 17778

East Asian (EAS) AF: 0.654 AC: 23979 AN: 36670

South Asian (SAS) AF: 0.389 AC: 24176 AN: 62202

European-Finnish (FIN) AF: 0.389 AC: 18864 AN: 48450

Middle Eastern (MID) AF: 0.368 AC: 1658 AN: 4502

European-Non Finnish (NFE) AF: 0.418 AC: 270606 AN: 647516

Other (OTH) AF: 0.449 AC: 18582 AN: 41386

GnomAD4 genome AF: 0.480 AC: 72920 AN: 151868 Hom.: 18118 Cov.: 31 AF XY: 0.476 AC XY: 35319 AN XY: 74190

African (AFR) AF: 0.615 AC: 25458 AN: 41416

American (AMR) AF: 0.468 AC: 7146 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1539 AN: 3470

East Asian (EAS) AF: 0.625 AC: 3230 AN: 5164

South Asian (SAS) AF: 0.397 AC: 1912 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 3967 AN: 10504

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28198 AN: 67926

Other (OTH) AF: 0.443 AC: 933 AN: 2106

Alfa AF: 0.442 Hom.: 11935

Bravo AF: 0.498

Asia WGS AF: 0.500 AC: 1737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=100/0	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: rs222852; hg19: chr17-7140606; COSMIC: COSV50035883; COSMIC: COSV50035883;