Variant 20-63961404-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_020713.3(ZNF512B):c.2332G>T(p.Ala778Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000209 in 1,611,332 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ZNF512B
NM_020713.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.78

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 -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007968932).

BP6

Variant 20-63961404-C-A is Benign according to our data. Variant chr20-63961404-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3049856.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF512B	NM_020713.3 linkuse as main transcript	c.2332G>T	p.Ala778Ser	missense_variant	16/17	ENST00000369888.6	NP_065764.1	Q96KM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF512B	ENST00000369888.6 linkuse as main transcript	c.2332G>T	p.Ala778Ser	missense_variant	16/17	1	NM_020713.3	ENSP00000358904.1		Q96KM6

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

165

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000337

AC:

AN:

248894

Hom.:

AF XY:

0.000252

AC XY:

AN XY:

134914

show subpopulations

Gnomad AFR exome

AF:

0.00458

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

171

AN:

1459016

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

725886

show subpopulations

Gnomad4 AFR exome

AF:

0.00433

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.00108

AC:

165

AN:

152316

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00380

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000460

Hom.:

Bravo

AF:

0.00136

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000371

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZNF512B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.015

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

M_CAP

Benign

0.0064

MetaRNN

Benign

0.0080

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

PrimateAI

Benign

0.36

PROVEAN

Benign

1.2

REVEL

Benign

0.053

Sift

Benign

0.32

Sift4G

Benign

0.35

Polyphen

0.014

Vest4

0.14

MVP

0.043

ClinPred

0.0056

GERP RS

4.3

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.3

Varity_R

0.021

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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