9-34972448-C-G

Variant names:

• chr9-34972448-C-G
• NM_015297.3:c.481C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015297.3(PHF24):​c.481C>G​(p.Arg161Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R161C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF24 NM_015297.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.69
• Publications: 0 publications found

Genes affected

PHF24 (HGNC:29180): (PHD finger protein 24) Predicted to enable metal ion binding activity. Predicted to act upstream of or within several processes, including detection of mechanical stimulus involved in sensory perception of pain; gamma-aminobutyric acid signaling pathway; and regulation of GABAergic synaptic transmission. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015297.3. 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
	PHF24	NM_015297.3	MANE Select	c.481C>G	p.Arg161Gly	missense	Exon 3 of 8	NP_056112.1	Q9UPV7
	PHF24	NM_001347982.1		c.481C>G	p.Arg161Gly	missense	Exon 3 of 8	NP_001334911.1
	PHF24	NM_001347983.2		c.481C>G	p.Arg161Gly	missense	Exon 3 of 8	NP_001334912.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF24	ENST00000242315.4	TSL:1 MANE Select	c.481C>G	p.Arg161Gly	missense	Exon 3 of 8	ENSP00000242315.3	Q9UPV7
	PHF24	ENST00000948628.1		c.481C>G	p.Arg161Gly	missense	Exon 3 of 8	ENSP00000618687.1
	PHF24	ENST00000476115.2	TSL:5	n.173C>G		non_coding_transcript_exon	Exon 3 of 8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.32	T
PhyloP100		5.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.60
MutPred		0.43		Loss of stability (P = 0.0375)
MVP		0.11
MPC		1.3
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.66
gMVP		0.60
Mutation Taster		=63/37	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

hg19: chr9-34972445;