chr9-34971432-G-A

Variant names:

• chr9-34971432-G-A
• rs775490664
• NM_015297.3:c.134G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395369.1(PHF24):​c.-117G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: PHF24 NM_001395369.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.01
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.084961504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395369.1. 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.134G>A	p.Arg45His	missense	Exon 2 of 8	NP_056112.1	Q9UPV7
	PHF24	NM_001395369.1		c.-117G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001382298.1
	PHF24	NM_001347982.1		c.134G>A	p.Arg45His	missense	Exon 2 of 8	NP_001334911.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF24	ENST00000242315.4	TSL:1 MANE Select	c.134G>A	p.Arg45His	missense	Exon 2 of 8	ENSP00000242315.3	Q9UPV7
	PHF24	ENST00000486477.1	TSL:1	n.228G>A		non_coding_transcript_exon	Exon 2 of 2
	PHF24	ENST00000948628.1		c.134G>A	p.Arg45His	missense	Exon 2 of 8	ENSP00000618687.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000401 AC: 10 AN: 249424 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000376 AC: 55 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27 AN XY: 727240

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

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1112012

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.000654 AC: 10 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.0000413 AC: 5

EpiCase AF: 0.0000545

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	0.086
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.84	T
PhyloP100		3.0
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.038
Sift	Uncertain	0.020	D
Sift4G	Benign	0.084	T
Polyphen		0.65	P
Vest4		0.074
MutPred		0.23		Loss of methylation at R45 (P = 0.0165)
MVP		0.11
MPC		0.46
ClinPred		0.16	T
GERP RS		4.9
Varity_R		0.083
gMVP		0.18
Mutation Taster		=96/4	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: rs775490664; hg19: chr9-34971429;