chr18-74631200-A-G

Position:

chr18-74631200-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017757.3(ZNF407):c.181A>G(p.Ser61Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,613,998 control chromosomes in the GnomAD database, including 453 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 (★★).

Frequency

Genomes: 𝑓 0.018 ( 43 hom., cov: 32)

Exomes 𝑓: 0.022 ( 410 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.412

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002408117).

BP6

Variant 18-74631200-A-G is Benign according to our data. Variant chr18-74631200-A-G is described in ClinVar as [Benign]. Clinvar id is 130817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-74631200-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0175 (2667/152308) while in subpopulation NFE AF= 0.0268 (1824/68018). AF 95% confidence interval is 0.0258. There are 43 homozygotes in gnomad4. There are 1268 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3 linkuse as main transcript	c.181A>G	p.Ser61Gly	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.181A>G	p.Ser61Gly	missense_variant	2/9	1	NM_017757.3	ENSP00000299687.4	Q9C0G0-1
ZNF407	ENST00000577538.5 linkuse as main transcript	c.181A>G	p.Ser61Gly	missense_variant	1/7	2		ENSP00000463270.1	Q9C0G0-2
ZNF407	ENST00000309902.10 linkuse as main transcript	c.181A>G	p.Ser61Gly	missense_variant	1/4	2		ENSP00000310359.5	Q9C0G0-3
ZNF407	ENST00000582337.5 linkuse as main transcript	c.181A>G	p.Ser61Gly	missense_variant	2/5	5		ENSP00000462348.1	Q9C0G0-3

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2667

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00480

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0234

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0268

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.0170

AC:

4239

AN:

249206

Hom.:

AF XY:

0.0172

AC XY:

2331

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.00387

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00533

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0261

Gnomad OTH exome

AF:

0.0220

GnomAD4 exome

AF:

0.0218

AC:

31900

AN:

1461690

Hom.:

410

Cov.:

AF XY:

0.0217

AC XY:

15770

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.0213

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00576

Gnomad4 FIN exome

AF:

0.0128

Gnomad4 NFE exome

AF:

0.0252

Gnomad4 OTH exome

AF:

0.0209

GnomAD4 genome

AF:

0.0175

AC:

2667

AN:

152308

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1268

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00479

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.0204

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0122

Gnomad4 NFE

AF:

0.0268

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.0232

Hom.:

Bravo

AF:

0.0183

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0213

AC:

ESP6500AA

AF:

0.00515

AC:

ESP6500EA

AF:

0.0273

AC:

223

ExAC

AF:

0.0170

AC:

2060

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0298

EpiControl

AF:

0.0270

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 16, 2015	- -

ZNF407-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 10, 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

0.067

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

DANN

Benign

0.93

DEOGEN2

Benign

0.025

.;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.35

.;T;T;T

MetaRNN

Benign

0.0024

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

L;L;L;L

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.66

.;N;.;N

REVEL

Benign

0.063

Sift

Benign

0.25

.;T;.;T

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.0020

B;B;B;B

Vest4

0.021

MPC

0.086

ClinPred

0.0039

GERP RS

-3.3

Varity_R

0.051

gMVP

0.039

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