rs746469742

Variant names:

• chr9-34971602-C-T
• rs746469742
• NM_015297.3:c.304C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-34971602-C-T
• chr9-34971602-C-A
• chr9-34971602-C-G

Variant summary

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

The NM_015297.3(PHF24):​c.304C>T​(p.Pro102Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: PHF24 NM_015297.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44
• 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.304C>T	p.Pro102Ser	missense	Exon 2 of 8	NP_056112.1	Q9UPV7
	PHF24	NM_001347982.1		c.304C>T	p.Pro102Ser	missense	Exon 2 of 8	NP_001334911.1
	PHF24	NM_001347983.2		c.304C>T	p.Pro102Ser	missense	Exon 2 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.304C>T	p.Pro102Ser	missense	Exon 2 of 8	ENSP00000242315.3	Q9UPV7
	PHF24	ENST00000948628.1		c.304C>T	p.Pro102Ser	missense	Exon 2 of 8	ENSP00000618687.1
	PHF24	ENST00000476115.2	TSL:5	n.135+256C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1111998

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.47	T
PhyloP100		7.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.24		Loss of catalytic residue at P101 (P = 0.0102)
MVP		0.25
MPC		0.91
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.31
gMVP		0.67
Mutation Taster		=19/81	disease causing

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: rs746469742; hg19: chr9-34971599;