Genetic Variant NM_001033561.2:c.2704G>A (chr17-28906494-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033561.2(PHF12):c.2704G>A(p.Asp902Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PHF12
NM_001033561.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: G2P

PHF12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10109106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF12	NM_001033561.2	MANE Select	c.2704G>A	p.Asp902Asn	missense	Exon 15 of 15	NP_001028733.1	Q96QT6-1
	PHF12	NM_001290131.2		c.*3541G>A		3_prime_UTR	Exon 11 of 11	NP_001277060.1	Q96QT6-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF12	ENST00000332830.9	TSL:2 MANE Select	c.2704G>A	p.Asp902Asn	missense	Exon 15 of 15	ENSP00000329933.4	Q96QT6-1
PHF12	ENST00000577226.5	TSL:1	c.*3541G>A		3_prime_UTR	Exon 11 of 11	ENSP00000465161.1	Q96QT6-5
PHF12	ENST00000930975.1		c.2743G>A	p.Asp915Asn	missense	Exon 16 of 16	ENSP00000601034.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453546

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33338

American (AMR)

AF:

0.00

AC:

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.00

AC:

AN:

39464

South Asian (SAS)

AF:

0.00

AC:

AN:

86042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1105612

Other (OTH)

AF:

0.00

AC:

AN:

59980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

PHF12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.10

MetaSVM

Uncertain

0.14

MutationAssessor

Benign

0.81

PhyloP100

3.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.73

REVEL

Uncertain

0.33

Sift

Benign

0.036

Sift4G

Benign

0.16

Polyphen

0.0010

Vest4

0.10

MutPred

0.13

Gain of MoRF binding (P = 0.0531)

MVP

0.52

MPC

0.25

ClinPred

0.69

GERP RS

3.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.11

gMVP

0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over