Variant chr17-28906258-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001033561.2(PHF12):c.2940G>C(p.Gln980His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

PHF12
NM_001033561.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.126

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16717455).

BS2

High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF12	NM_001033561.2 link	c.2940G>C	p.Gln980His	missense_variant	15/15	ENST00000332830.9	NP_001028733.1	Q96QT6-1
PHF12	NM_001290131.2 link	c.*3777G>C		3_prime_UTR_variant	11/11		NP_001277060.1	Q96QT6-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PHF12	ENST00000332830.9 link	c.2940G>C	p.Gln980His	missense_variant	15/15	2	NM_001033561.2	ENSP00000329933.4	Q96QT6-1
PHF12	ENST00000577226 link	c.*3777G>C		3_prime_UTR_variant	11/11	1		ENSP00000465161.1	Q96QT6-5
PHF12	ENST00000589176.1 link	n.*475G>C		non_coding_transcript_exon_variant	6/6	5		ENSP00000465255.1	K7EJN7
PHF12	ENST00000589176.1 link	n.*475G>C		3_prime_UTR_variant	6/6	5		ENSP00000465255.1	K7EJN7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251176

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461336

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

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

Jul 15, 2021

The c.2940G>C (p.Q980H) alteration is located in exon 15 (coding exon 15) of the PHF12 gene. This alteration results from a G to C substitution at nucleotide position 2940, causing the glutamine (Q) at amino acid position 980 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.094

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.17

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.26

REVEL

Benign

0.29

Sift

Benign

0.039

Sift4G

Benign

0.073

Polyphen

0.83

Vest4

0.17

MutPred

0.25

Loss of stability (P = 0.0509);

MVP

0.42

MPC

0.32

ClinPred

0.16

GERP RS

-0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.42

Splicing

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