rs74861823

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_017757.3(ZNF407):c.490A>G(p.Arg164Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,613,966 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.503

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomalies
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ZNF407 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027053654).

BP6

Variant 18-74631509-A-G is Benign according to our data. Variant chr18-74631509-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 437370.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3 link	c.490A>G	p.Arg164Gly	missense_variant	Exon 2 of 9	ENST00000299687.10	NP_060227.2	Q9C0G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF407	ENST00000299687.10 link	c.490A>G	p.Arg164Gly	missense_variant	Exon 2 of 9	1	NM_017757.3	ENSP00000299687.4	Q9C0G0-1
ZNF407	ENST00000577538.5 link	c.490A>G	p.Arg164Gly	missense_variant	Exon 1 of 7	2		ENSP00000463270.1	Q9C0G0-2
ZNF407	ENST00000309902.10 link	c.490A>G	p.Arg164Gly	missense_variant	Exon 1 of 4	2		ENSP00000310359.5	Q9C0G0-3
ZNF407	ENST00000582337.5 link	c.490A>G	p.Arg164Gly	missense_variant	Exon 2 of 5	5		ENSP00000462348.1	Q9C0G0-3

Frequencies

GnomAD3 genomes

AF:

0.00287

AC:

437

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000759

AC:

189

AN:

249168

AF XY:

0.000577

show subpopulations

Gnomad AFR exome

AF:

0.00905

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000324

AC:

474

AN:

1461620

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

197

AN XY:

727086

show subpopulations

African (AFR)

AF:

0.00911

AC:

305

AN:

33480

American (AMR)

AF:

0.000648

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00195

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

1111870

Other (OTH)

AF:

0.000729

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00287

AC:

437

AN:

152346

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00986

AC:

410

AN:

41564

American (AMR)

AF:

0.000849

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68040

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00315

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00988

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000944

AC:

114

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZNF407: BP4 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 19, 2017

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.9

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.019

.;.;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.66

.;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.76

N;N;N;N

PhyloP100

0.50

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.50

.;N;.;N

REVEL

Benign

0.098

Sift

Benign

0.32

.;T;.;T

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.090

MVP

0.082

MPC

0.11

ClinPred

0.00054

GERP RS

-1.9

PromoterAI

0.0017

Neutral

(source)

Varity_R

0.077

gMVP

0.12

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over