Variant 17-28912883-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001033561.2(PHF12):c.1688G>A(p.Arg563Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,612,446 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 2 hom. )

Consequence

PHF12
NM_001033561.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

Variant links:

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]

PHF12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0193834).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF12	NM_001033561.2 link	c.1688G>A	p.Arg563Gln	missense_variant	9/15	ENST00000332830.9	NP_001028733.1	Q96QT6-1
PHF12	NM_001290131.2 link	c.1688G>A	p.Arg563Gln	missense_variant	9/11		NP_001277060.1	Q96QT6-5
PHF12	NM_020889.3 link	c.1688G>A	p.Arg563Gln	missense_variant	9/9		NP_065940.1	Q96QT6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF12	ENST00000332830.9 link	c.1688G>A	p.Arg563Gln	missense_variant	9/15	2	NM_001033561.2	ENSP00000329933.4		Q96QT6-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000148

AC:

AN:

250138

Hom.:

AF XY:

0.000215

AC XY:

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000657

AC:

AN:

1460236

Hom.:

Cov.:

AF XY:

0.0000978

AC XY:

AN XY:

726172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000905

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.000198

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.1688G>A (p.R563Q) alteration is located in exon 9 (coding exon 9) of the PHF12 gene. This alteration results from a G to A substitution at nucleotide position 1688, causing the arginine (R) at amino acid position 563 to be replaced by a glutamine (Q). 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

0.071

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

T;.;T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.081

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

-0.11

N;N;.;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.090

N;.;.;N

REVEL

Uncertain

0.30

Sift

Benign

0.29

T;.;.;T

Sift4G

Benign

0.48

T;T;.;T

Polyphen

0.013

B;.;.;B

Vest4

0.23

MutPred

0.045

Gain of glycosylation at T560 (P = 0.0696);Gain of glycosylation at T560 (P = 0.0696);.;Gain of glycosylation at T560 (P = 0.0696);

MVP

0.44

MPC

0.29

ClinPred

0.029

GERP RS

5.7

Varity_R

0.083

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over