Variant chr2-27621162-G-A 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_032434.4(ZNF512):c.1405G>A(p.Val469Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ZNF512
NM_032434.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

ZNF512 (HGNC:29380): (zinc finger protein 512) This gene encodes a protein containing four putative zinc finger motifs. Zinc finger motifs may bind to proteins or nucleic acids. Zinc finger-containing proteins are involved in a variety of processes, including regulation of transcription. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Sep 2012]

ZNF512 links:

Genome browser will be placed here

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=0.031308115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF512	NM_032434.4 linkuse as main transcript	c.1405G>A	p.Val469Ile	missense_variant	14/14	ENST00000355467.6	NP_115810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF512	ENST00000355467.6 linkuse as main transcript	c.1405G>A	p.Val469Ile	missense_variant	14/14	2	NM_032434.4	ENSP00000347648	P3	Q96ME7-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000179

AC:

AN:

250864

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000218

AC:

318

AN:

1461456

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

155

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000210

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000258

Hom.:

Bravo

AF:

0.000246

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Mar 07, 2023

The c.1405G>A (p.V469I) alteration is located in exon 14 (coding exon 14) of the ZNF512 gene. This alteration results from a G to A substitution at nucleotide position 1405, causing the valine (V) at amino acid position 469 to be replaced by an isoleucine (I). 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

0.079

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.013

.;.;.;T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

.;T;T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.031

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

.;.;.;.;N

MutationTaster

Benign

0.73

N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.11

.;N;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.88

.;T;T;T;T

Sift4G

Benign

0.88

T;T;T;T;T

Polyphen

0.010

.;.;.;.;B

Vest4

0.020

MVP

0.043

MPC

1.3

ClinPred

0.046

GERP RS

3.4

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.023

gMVP

0.094

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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