chr9-34971375-A-T

Variant names:

• chr9-34971375-A-T
• NM_015297.3:c.77A>T

Variant summary

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

The NM_001395369.1(PHF24):​c.-174A>T variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF24 NM_001395369.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25

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.77A>T	p.Asp26Val	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.77A>T	p.Asp26Val	missense_variant	Exon 2 of 8	1	NM_015297.3	ENSP00000242315.3
PHF24	ENST00000486477.1	n.171A>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
PHF24	ENST00000476115.2	n.135+29A>T		intron_variant	Intron 2 of 7	5

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

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.77A>T (p.D26V) alteration is located in exon 2 (coding exon 1) of the PHF24 gene. This alteration results from a A to T substitution at nucleotide position 77, causing the aspartic acid (D) at amino acid position 26 to be replaced by a valine (V). 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	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.57	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.053	T
Polyphen		0.93	P
Vest4		0.65
MutPred		0.35		Gain of sheet (P = 0.0166);
MVP		0.043
MPC		1.4
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.23
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -29

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: chr9-34971372;