rs374283851

Variant names:

• chr17-7236244-C-T
• rs374283851
• NM_024297.3:c.683G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7236244-C-T
• chr17-7236244-C-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024297.3(PHF23):​c.683G>A​(p.Arg228Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R228W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: PHF23 NM_024297.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049255073).
• BS2: High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024297.3. 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
	PHF23	NM_024297.3	MANE Select	c.683G>A	p.Arg228Gln	missense	Exon 4 of 5	NP_077273.2	Q9BUL5-1
	PHF23	NM_001284518.2		c.671G>A	p.Arg224Gln	missense	Exon 4 of 5	NP_001271447.1	Q9BUL5-4
	PHF23	NM_001284517.2		c.482G>A	p.Arg161Gln	missense	Exon 4 of 5	NP_001271446.1	Q9BUL5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF23	ENST00000320316.8	TSL:1 MANE Select	c.683G>A	p.Arg228Gln	missense	Exon 4 of 5	ENSP00000322579.3	Q9BUL5-1
	PHF23	ENST00000454255.6	TSL:2	c.671G>A	p.Arg224Gln	missense	Exon 4 of 5	ENSP00000414607.2	Q9BUL5-4
	PHF23	ENST00000571362.5	TSL:2	c.482G>A	p.Arg161Gln	missense	Exon 4 of 5	ENSP00000460738.1	Q9BUL5-3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000443 AC: 11 AN: 248562 AF XY: 0.0000445

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000500 AC: 73 AN: 1461158 Hom.: 0 Cov.: 34 AF XY: 0.0000578 AC XY: 42 AN XY: 726846

African (AFR) AF: 0.0000299 AC: 1 AN: 33446

American (AMR) AF: 0.000157 AC: 7 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86176

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111632

Other (OTH) AF: 0.0000994 AC: 6 AN: 60344

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74484

African (AFR) AF: 0.0000241 AC: 1 AN: 41554

American (AMR) AF: 0.000131 AC: 2 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000831

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000263 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000414 AC: 5

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.077	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.055
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.14
MVP		0.082
MPC		1.1
ClinPred		0.086	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.49
Mutation Taster		=97/3	polymorphism

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: rs374283851; hg19: chr17-7139563; COSMIC: COSV50034578; COSMIC: COSV50034578;