Variant rs34141917 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_017757.3(ZNF407):c.4106G>A(p.Gly1369Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,613,970 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.39

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051732957).

BP6

Variant 18-74635125-G-A is Benign according to our data. Variant chr18-74635125-G-A is described in ClinVar as [Benign]. Clinvar id is 437364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3 linkuse as main transcript	c.4106G>A	p.Gly1369Asp	missense_variant	2/9	ENST00000299687.10	NP_060227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10 linkuse as main transcript	c.4106G>A	p.Gly1369Asp	missense_variant	2/9	1	NM_017757.3	ENSP00000299687	P2	Q9C0G0-1
ZNF407	ENST00000577538.5 linkuse as main transcript	c.4106G>A	p.Gly1369Asp	missense_variant	1/7	2		ENSP00000463270	A2	Q9C0G0-2
ZNF407	ENST00000309902.10 linkuse as main transcript	c.4106G>A	p.Gly1369Asp	missense_variant	1/4	2		ENSP00000310359		Q9C0G0-3
ZNF407	ENST00000582337.5 linkuse as main transcript	c.4106G>A	p.Gly1369Asp	missense_variant	2/5	5		ENSP00000462348		Q9C0G0-3

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

388

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000662

AC:

165

AN:

249088

Hom.:

AF XY:

0.000511

AC XY:

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.00949

Gnomad AMR exome

AF:

0.000377

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:

0.00000886

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000228

AC:

333

AN:

1461672

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00825

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.00256

AC:

390

AN:

152298

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00895

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000324

Hom.:

Bravo

AF:

0.00267

ESP6500AA

AF:

0.00716

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000803

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 17, 2017

- -

ZNF407-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.069

.;.;.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.089

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.64

.;T;T;T

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

M;M;M;M

MutationTaster

Benign

0.79

D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

.;N;.;N

REVEL

Benign

0.14

Sift

Benign

0.069

.;T;.;T

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.36

B;B;B;B

Vest4

0.20

MVP

0.18

MPC

0.12

ClinPred

0.013

GERP RS

3.3

Varity_R

0.14

gMVP

0.21

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