NM_017757.3:c.6301G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_017757.3(ZNF407):c.6301G>A(p.Gly2101Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,605,982 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4B:1

Conservation

PhyloP100: 9.12

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:

ENSG00000278607 (HGNC:):

ENSG00000278607 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29432526).

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3 link	c.6301G>A	p.Gly2101Ser	missense_variant	Exon 9 of 9	ENST00000299687.10	NP_060227.2	Q9C0G0-1
ZNF407	NM_001384475.1 link	c.6301G>A	p.Gly2101Ser	missense_variant	Exon 9 of 9		NP_001371404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10 link	c.6301G>A	p.Gly2101Ser	missense_variant	Exon 9 of 9	1	NM_017757.3	ENSP00000299687.4		Q9C0G0-1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000283

AC:

AN:

229782

AF XY:

0.000304

show subpopulations

Gnomad AFR exome

AF:

0.000226

Gnomad AMR exome

AF:

0.000611

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.000201

AC:

292

AN:

1453688

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

152

AN XY:

722396

show subpopulations

African (AFR)

AF:

0.000360

AC:

AN:

33312

American (AMR)

AF:

0.000735

AC:

AN:

43556

Ashkenazi Jewish (ASJ)

AF:

0.0000386

AC:

AN:

25882

East Asian (EAS)

AF:

0.00

AC:

AN:

39232

South Asian (SAS)

AF:

0.000165

AC:

AN:

84720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52438

Middle Eastern (MID)

AF:

0.00278

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000170

AC:

188

AN:

1108660

Other (OTH)

AF:

0.000482

AC:

AN:

60124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000269

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41566

American (AMR)

AF:

0.000588

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68024

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

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:

0.000279

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.000354

AC:

ExAC

AF:

0.000231

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4Benign:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 12, 2024

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Reported previously in the heterozygous state in a proband from a cohort of individuals with intellectual disability; inherited form an unaffected mother (PMID: 25356899); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25356899) -

not specified

Uncertain:1

Apr 23, 2015

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Uncertain:1

Apr 06, 2016

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ZNF407-related disorder

Benign:1

Sep 17, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.2

PhyloP100

9.1

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.51

MVP

0.39

MPC

0.64

ClinPred

0.10

GERP RS

4.7

Varity_R

0.24

gMVP

0.13

Mutation Taster

=30/70

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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