17-28912695-G-T

Position:

• chr17-28912695-G-T

Variant summary

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

The NM_001033561.2(PHF12):​c.1876C>A​(p.Pro626Thr) 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. 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: 2.12

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=0.10903406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF12	NM_001033561.2	c.1876C>A	p.Pro626Thr	missense_variant	9/15	ENST00000332830.9	NP_001028733.1
PHF12	NM_001290131.2	c.1876C>A	p.Pro626Thr	missense_variant	9/11		NP_001277060.1
PHF12	NM_020889.3	c.1876C>A	p.Pro626Thr	missense_variant	9/9		NP_065940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF12	ENST00000332830.9	c.1876C>A	p.Pro626Thr	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

Oct 29, 2021

The c.1876C>A (p.P626T) alteration is located in exon 9 (coding exon 9) of the PHF12 gene. This alteration results from a C to A substitution at nucleotide position 1876, causing the proline (P) at amino acid position 626 to be replaced by a threonine (T). 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	0.060
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.072	T;.;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.86	D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Uncertain	0.049	D
MutationAssessor	Benign	0.34	N;N;.;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.24	N;.;.;N
REVEL	Uncertain	0.30
Sift	Benign	0.50	T;.;.;T
Sift4G	Benign	0.45	T;T;.;T
Polyphen		0.0030	B;.;.;B
Vest4		0.24
MutPred		0.16		Loss of catalytic residue at P625 (P = 0.0258);Loss of catalytic residue at P625 (P = 0.0258);.;Loss of catalytic residue at P625 (P = 0.0258);
MVP		0.17
MPC		0.28
ClinPred		0.32	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
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: chr17-27239713;