chr17-28912791-G-C

Position:

• chr17-28912791-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033561.2(PHF12):​c.1780C>G​(p.Gln594Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: PHF12 NM_001033561.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

Genes affected

PHF12 (HGNC:20816): (PHD finger protein 12) Enables phosphatidylinositol binding activity and transcription corepressor activity. Involved in negative regulation of transcription, DNA-templated. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of Sin3 complex and transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12422392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF12	NM_001033561.2	c.1780C>G	p.Gln594Glu	missense_variant	9/15	ENST00000332830.9	NP_001028733.1
PHF12	NM_001290131.2	c.1780C>G	p.Gln594Glu	missense_variant	9/11		NP_001277060.1
PHF12	NM_020889.3	c.1780C>G	p.Gln594Glu	missense_variant	9/9		NP_065940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF12	ENST00000332830.9	c.1780C>G	p.Gln594Glu	missense_variant	9/15	2	NM_001033561.2	ENSP00000329933.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 08, 2024

The c.1780C>G (p.Q594E) alteration is located in exon 9 (coding exon 9) of the PHF12 gene. This alteration results from a C to G substitution at nucleotide position 1780, causing the glutamine (Q) at amino acid position 594 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.077	T;.;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.021
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.20	N;N;.;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.10	N;.;.;N
REVEL	Benign	0.23
Sift	Benign	0.96	T;.;.;T
Sift4G	Benign	1.0	T;T;.;T
Polyphen		0.0070	B;.;.;B
Vest4		0.36
MutPred		0.22		Gain of relative solvent accessibility (P = 0.2363);Gain of relative solvent accessibility (P = 0.2363);.;Gain of relative solvent accessibility (P = 0.2363);
MVP		0.50
MPC		0.28
ClinPred		0.29	T
GERP RS		5.1
Varity_R		0.14
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

LitVar

Other links and lift over

dbSNP: rs2039986948; hg19: chr17-27239809;