Variant chr17-28910119-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001290131.2(PHF12):c.2466C>T(p.Ser822Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,500,378 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

PHF12
NM_001290131.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.186

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-28910119-G-A is Benign according to our data. Variant chr17-28910119-G-A is described in ClinVar as [Benign]. Clinvar id is 3046281.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.186 with no splicing effect.

BS2

High AC in GnomAd4 at 316 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF12	NM_001033561.2 link	c.2359+107C>T		intron_variant		ENST00000332830.9	NP_001028733.1	Q96QT6-1
PHF12	NM_001290131.2 link	c.2466C>T	p.Ser822Ser	synonymous_variant	11/11		NP_001277060.1	Q96QT6-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF12	ENST00000332830.9 link	c.2359+107C>T		intron_variant		2	NM_001033561.2	ENSP00000329933.4		Q96QT6-1

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

314

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000560

AC:

140

AN:

249842

Hom.:

AF XY:

0.000444

AC XY:

AN XY:

135124

show subpopulations

Gnomad AFR exome

AF:

0.00797

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000205

AC:

277

AN:

1348102

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

120

AN XY:

677152

show subpopulations

Gnomad4 AFR exome

AF:

0.00723

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000388

GnomAD4 genome

AF:

0.00208

AC:

316

AN:

152276

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00729

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.00216

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PHF12-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.55

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