Variant 17-28912612-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001033561.2(PHF12):c.1959G>A(p.Pro653Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,614,164 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 66 hom. )

Consequence

PHF12
NM_001033561.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.13

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 17-28912612-C-T is Benign according to our data. Variant chr17-28912612-C-T is described in ClinVar as [Benign]. Clinvar id is 790330.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-28912612-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.13 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00259 (394/152270) while in subpopulation SAS AF= 0.0224 (108/4824). AF 95% confidence interval is 0.019. There are 3 homozygotes in gnomad4. There are 222 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 394 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF12	NM_001033561.2 link	c.1959G>A	p.Pro653Pro	synonymous_variant	9/15	ENST00000332830.9	NP_001028733.1	Q96QT6-1
PHF12	NM_001290131.2 link	c.1959G>A	p.Pro653Pro	synonymous_variant	9/11		NP_001277060.1	Q96QT6-5
PHF12	NM_020889.3 link	c.1959G>A	p.Pro653Pro	synonymous_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.1959G>A	p.Pro653Pro	synonymous_variant	9/15	2	NM_001033561.2	ENSP00000329933.4		Q96QT6-1

Frequencies

GnomAD3 genomes

AF:

0.00259

AC:

394

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0224

Gnomad FIN

AF:

0.00425

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00510

AC:

1283

AN:

251474

Hom.:

AF XY:

0.00615

AC XY:

836

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00774

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0243

Gnomad FIN exome

AF:

0.00388

Gnomad NFE exome

AF:

0.00275

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00324

AC:

4740

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

2826

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.00899

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0239

Gnomad4 FIN exome

AF:

0.00432

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.00321

GnomAD4 genome

AF:

0.00259

AC:

394

AN:

152270

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.00425

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.00180

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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