9-34971632-G-C

Variant names:

• chr9-34971632-G-C
• NM_015297.3:c.334G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015297.3(PHF24):​c.334G>C​(p.Asp112His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 1.81

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038731456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF24	NM_015297.3	c.334G>C	p.Asp112His	missense_variant	Exon 2 of 8	ENST00000242315.4	NP_056112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF24	ENST00000242315.4	c.334G>C	p.Asp112His	missense_variant	Exon 2 of 8	1	NM_015297.3	ENSP00000242315.3
PHF24	ENST00000476115.2	n.135+286G>C		intron_variant	Intron 2 of 7	5
PHF24	ENST00000486477.1	n.*115G>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.334G>C (p.D112H) alteration is located in exon 2 (coding exon 1) of the PHF24 gene. This alteration results from a G to C substitution at nucleotide position 334, causing the aspartic acid (D) at amino acid position 112 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.025
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.11
Sift	Benign	0.17	T
Sift4G	Benign	0.71	T
Polyphen		0.0050	B
Vest4		0.14
MutPred		0.15		Loss of solvent accessibility (P = 0.0217);
MVP		0.043
MPC		0.44
ClinPred		0.20	T
GERP RS		3.0
Varity_R		0.067
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-34971629;