Variant 7-6691983-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016265.4(ZNF12):c.959C>A(p.Thr320Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 2.49

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31949604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF12	NM_016265.4 link	c.959C>A	p.Thr320Lys	missense_variant	5/5	ENST00000405858.6	NP_057349.2	P17014-1
ZNF12	NM_006956.3 link	c.845C>A	p.Thr282Lys	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.959C>A	p.Thr320Lys	missense_variant	5/5	1	NM_016265.4	ENSP00000385939.1	P17014-1
ZNF12	ENST00000404360.5 link	c.737C>A	p.Thr246Lys	missense_variant	5/5	1		ENSP00000384405.1	P17014-4
ZNF12	ENST00000342651.9 link	c.845C>A	p.Thr282Lys	missense_variant	6/6	2		ENSP00000344745.5	P17014-5
ENSG00000228010	ENST00000366167.2 link	n.136-16318G>T		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727230

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 27, 2024

The c.959C>A (p.T320K) alteration is located in exon 5 (coding exon 4) of the ZNF12 gene. This alteration results from a C to A substitution at nucleotide position 959, causing the threonine (T) at amino acid position 320 to be replaced by a lysine (K). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

.;T;.

Eigen

Benign

-0.032

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.064

T;T;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;L;.

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0050

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.97, 0.99

.;D;D

Vest4

0.46

MutPred

0.32

.;Gain of methylation at T320 (P = 0.0053);.;

MVP

0.34

MPC

0.82

ClinPred

0.99

GERP RS

1.3

Varity_R

0.23

gMVP

0.14

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