NM_015297.3:c.482G>T

Variant names:

• chr9-34972449-G-T
• rs754208132
• NM_015297.3:c.482G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015297.3(PHF24):​c.482G>T​(p.Arg161Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHF24 NM_015297.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.68

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF24	NM_015297.3	c.482G>T	p.Arg161Leu	missense_variant	Exon 3 of 8	ENST00000242315.4	NP_056112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF24	ENST00000242315.4	c.482G>T	p.Arg161Leu	missense_variant	Exon 3 of 8	1	NM_015297.3	ENSP00000242315.3
PHF24	ENST00000476115.2	n.174G>T		non_coding_transcript_exon_variant	Exon 3 of 8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249402 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135310

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727192

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.46	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.019	D
Polyphen		0.99	D
Vest4		0.57
MutPred		0.42		Gain of sheet (P = 0.0477);
MVP		0.068
MPC		1.3
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.63
gMVP		0.62

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: rs754208132; hg19: chr9-34972446;