Variant 7-6690856-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016265.4(ZNF12):c.2086C>T(p.Leu696Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,607,972 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

ZNF12
NM_016265.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.579

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1155459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF12	NM_016265.4 link	c.2086C>T	p.Leu696Phe	missense_variant	5/5	ENST00000405858.6	NP_057349.2	P17014-1
ZNF12	NM_006956.3 link	c.1972C>T	p.Leu658Phe	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.2086C>T	p.Leu696Phe	missense_variant	5/5	1	NM_016265.4	ENSP00000385939.1	P17014-1
ZNF12	ENST00000404360.5 link	c.1864C>T	p.Leu622Phe	missense_variant	5/5	1		ENSP00000384405.1	P17014-4
ZNF12	ENST00000342651.9 link	c.1972C>T	p.Leu658Phe	missense_variant	6/6	2		ENSP00000344745.5	P17014-5
ENSG00000228010	ENST00000366167.2 link	n.136-17445G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

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:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000822

AC:

AN:

243254

Hom.:

AF XY:

0.0000910

AC XY:

AN XY:

131934

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000890

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000473

Gnomad NFE exome

AF:

0.000137

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000191

AC:

278

AN:

1455774

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

131

AN XY:

723788

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000943

Gnomad4 NFE exome

AF:

0.000227

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.000217

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000157

Hom.:

Bravo

AF:

0.000302

ExAC

AF:

0.0000910

AC:

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

Dec 31, 2023

The c.2086C>T (p.L696F) alteration is located in exon 5 (coding exon 4) of the ZNF12 gene. This alteration results from a C to T substitution at nucleotide position 2086, causing the leucine (L) at amino acid position 696 to be replaced by a phenylalanine (F). 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

0.088

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

.;T;.

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

-0.040

.;N;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.75

N;N;N

REVEL

Benign

0.093

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.21

MVP

0.16

MPC

0.77

ClinPred

0.19

GERP RS

4.2

Varity_R

0.097

gMVP

0.085

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