Variant 7-6690990-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016265.4(ZNF12):c.1952A>G(p.His651Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF12
NM_016265.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

Variant links:

Genes affected

ZNF12 (HGNC:12902): (zinc finger protein 12) This gene is a member of the krueppel C2H2-type zinc-finger protein family and encodes a protein with eight C2H2-type zinc fingers and a KRAB domain. This nuclear protein is involved in developmental control of gene expression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ZNF12 links:

ENSG00000228010 (HGNC:):

ENSG00000228010 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF12	NM_016265.4 link	c.1952A>G	p.His651Arg	missense_variant	5/5	ENST00000405858.6	NP_057349.2	P17014-1
ZNF12	NM_006956.3 link	c.1838A>G	p.His613Arg	missense_variant	6/6		NP_008887.2	P17014-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF12	ENST00000405858.6 link	c.1952A>G	p.His651Arg	missense_variant	5/5	1	NM_016265.4	ENSP00000385939.1	P17014-1
ZNF12	ENST00000404360.5 link	c.1730A>G	p.His577Arg	missense_variant	5/5	1		ENSP00000384405.1	P17014-4
ZNF12	ENST00000342651.9 link	c.1838A>G	p.His613Arg	missense_variant	6/6	2		ENSP00000344745.5	P17014-5
ENSG00000228010	ENST00000366167.2 link	n.136-17311T>C		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727204

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 25, 2024

The c.1952A>G (p.H651R) alteration is located in exon 5 (coding exon 4) of the ZNF12 gene. This alteration results from a A to G substitution at nucleotide position 1952, causing the histidine (H) at amino acid position 651 to be replaced by an arginine (R). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

.;T;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.68

T;T;T

M_CAP

Pathogenic

0.41

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Pathogenic

0.89

MutationAssessor

Pathogenic

3.8

.;H;.

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-6.8

D;D;D

REVEL

Pathogenic

0.81

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.84

MutPred

0.78

.;Gain of MoRF binding (P = 0.0104);.;

MVP

0.96

MPC

0.82

ClinPred

1.0

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.74

gMVP

0.65

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over