18-74631225-A-G

Position:

chr18-74631225-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_017757.3(ZNF407):c.206A>G(p.Asn69Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 1,613,950 control chromosomes in the GnomAD database, including 3,480 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.072 ( 460 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3020 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

ZNF407 (HGNC:19904): (zinc finger protein 407) This gene encodes a zinc finger protein whose exact function is not known. It may be involved in transcriptional regulation. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ZNF407 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016692579).

BP6

Variant 18-74631225-A-G is Benign according to our data. Variant chr18-74631225-A-G is described in ClinVar as [Benign]. Clinvar id is 130818.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3 linkuse as main transcript	c.206A>G	p.Asn69Ser	missense_variant	2/9	ENST00000299687.10	NP_060227.2	Q9C0G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF407	ENST00000299687.10 linkuse as main transcript	c.206A>G	p.Asn69Ser	missense_variant	2/9	1	NM_017757.3	ENSP00000299687.4	Q9C0G0-1
ZNF407	ENST00000577538.5 linkuse as main transcript	c.206A>G	p.Asn69Ser	missense_variant	1/7	2		ENSP00000463270.1	Q9C0G0-2
ZNF407	ENST00000309902.10 linkuse as main transcript	c.206A>G	p.Asn69Ser	missense_variant	1/4	2		ENSP00000310359.5	Q9C0G0-3
ZNF407	ENST00000582337.5 linkuse as main transcript	c.206A>G	p.Asn69Ser	missense_variant	2/5	5		ENSP00000462348.1	Q9C0G0-3

Frequencies

GnomAD3 genomes

AF:

0.0713

AC:

10850

AN:

152188

Hom.:

453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0470

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.0356

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0408

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0571

Gnomad OTH

AF:

0.0555

GnomAD3 exomes

AF:

0.0596

AC:

14839

AN:

249162

Hom.:

560

AF XY:

0.0618

AC XY:

8354

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.0287

Gnomad ASJ exome

AF:

0.0424

Gnomad EAS exome

AF:

0.0391

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0446

Gnomad NFE exome

AF:

0.0569

Gnomad OTH exome

AF:

0.0570

GnomAD4 exome

AF:

0.0605

AC:

88464

AN:

1461644

Hom.:

3020

Cov.:

AF XY:

0.0621

AC XY:

45128

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.0311

Gnomad4 ASJ exome

AF:

0.0434

Gnomad4 EAS exome

AF:

0.0211

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0446

Gnomad4 NFE exome

AF:

0.0592

Gnomad4 OTH exome

AF:

0.0633

GnomAD4 genome

AF:

0.0715

AC:

10891

AN:

152306

Hom.:

460

Cov.:

AF XY:

0.0710

AC XY:

5286

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0470

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.0363

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0408

Gnomad4 NFE

AF:

0.0571

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0611

Hom.:

604

Bravo

AF:

0.0730

TwinsUK

AF:

0.0645

AC:

239

ALSPAC

AF:

0.0620

AC:

239

ESP6500AA

AF:

0.120

AC:

444

ESP6500EA

AF:

0.0583

AC:

476

ExAC

AF:

0.0627

AC:

7573

Asia WGS

AF:

0.0910

AC:

315

AN:

3478

EpiCase

AF:

0.0603

EpiControl

AF:

0.0544

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

ZNF407-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 05, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

DANN

Benign

0.44

DEOGEN2

Benign

0.032

.;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.70

.;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

L;L;L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.97

.;N;.;N

REVEL

Benign

0.068

Sift

Benign

0.32

.;T;.;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.0040

B;B;B;B

Vest4

0.0090

MPC

0.069

ClinPred

0.0078

GERP RS

0.12

Varity_R

0.027

gMVP

0.054

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