Variant 7-6691414-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016265.4(ZNF12):c.1528A>G(p.Ile510Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000806 in 1,613,840 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00083 ( 1 hom. )

Consequence

ZNF12
NM_016265.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.18

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_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028680354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF12	NM_016265.4 link	c.1528A>G	p.Ile510Val	missense_variant	5/5	ENST00000405858.6	NP_057349.2	P17014-1
ZNF12	NM_006956.3 link	c.1414A>G	p.Ile472Val	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.1528A>G	p.Ile510Val	missense_variant	5/5	1	NM_016265.4	ENSP00000385939.1	P17014-1
ZNF12	ENST00000404360.5 link	c.1306A>G	p.Ile436Val	missense_variant	5/5	1		ENSP00000384405.1	P17014-4
ZNF12	ENST00000342651.9 link	c.1414A>G	p.Ile472Val	missense_variant	6/6	2		ENSP00000344745.5	P17014-5
ENSG00000228010	ENST00000366167.2 link	n.136-16887T>C		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000605

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000475

AC:

119

AN:

250308

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.000191

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000980

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000827

AC:

1209

AN:

1461716

Hom.:

Cov.:

AF XY:

0.000817

AC XY:

594

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000605

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000842

Hom.:

Bravo

AF:

0.000510

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000363

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000771

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

Oct 12, 2021

The c.1528A>G (p.I510V) 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 1528, causing the isoleucine (I) at amino acid position 510 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.1

DANN

Benign

0.78

DEOGEN2

Benign

0.020

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00023

LIST_S2

Benign

0.20

T;T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.41

.;N;.

PrimateAI

Benign

0.39

PROVEAN

Benign

0.39

N;N;N

REVEL

Benign

0.034

Sift

Benign

0.59

T;T;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.046

MVP

0.11

MPC

0.16

ClinPred

0.014

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.033

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