Variant 20-63959917-C-T 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_020713.3(ZNF512B):c.2650G>A(p.Val884Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,601,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF512B
NM_020713.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.141

Variant links:

Genes affected

ZNF512B (HGNC:29212): (zinc finger protein 512B) Predicted to enable DNA binding activity and metal ion binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF512B 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=0.02931571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF512B	NM_020713.3 linkuse as main transcript	c.2650G>A	p.Val884Met	missense_variant	17/17	ENST00000369888.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF512B	ENST00000369888.6 linkuse as main transcript	c.2650G>A	p.Val884Met	missense_variant	17/17	1	NM_020713.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000417

AC:

AN:

239880

Hom.:

AF XY:

0.00000762

AC XY:

AN XY:

131300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000912

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1449616

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

721174

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:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Sep 20, 2023

The c.2650G>A (p.V884M) alteration is located in exon 17 (coding exon 16) of the ZNF512B gene. This alteration results from a G to A substitution at nucleotide position 2650, causing the valine (V) at amino acid position 884 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.65

M_CAP

Benign

0.015

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.60

REVEL

Benign

0.061

Sift

Benign

0.042

Sift4G

Benign

0.11

Polyphen

0.018

Vest4

0.058

MutPred

0.096

Loss of methylation at K883 (P = 0.0223);

MVP

0.082

ClinPred

0.063

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.060

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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