rs150419019

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017757.3(ZNF407):c.6007G>A(p.Glu2003Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,612,346 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 58 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 9.01

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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042485595).

BP6

Variant 18-75063728-G-A is Benign according to our data. Variant chr18-75063728-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3 link	c.6007G>A	p.Glu2003Lys	missense_variant	Exon 9 of 9	ENST00000299687.10	NP_060227.2	Q9C0G0-1
ZNF407	NM_001384475.1 link	c.6007G>A	p.Glu2003Lys	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.6007G>A	p.Glu2003Lys	missense_variant	Exon 9 of 9	1	NM_017757.3	ENSP00000299687.4		Q9C0G0-1

Frequencies

GnomAD3 genomes

AF:

0.00578

AC:

880

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.0339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00592

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00569

AC:

1400

AN:

245890

AF XY:

0.00589

show subpopulations

Gnomad AFR exome

AF:

0.000867

Gnomad AMR exome

AF:

0.00215

Gnomad ASJ exome

AF:

0.000904

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0287

Gnomad NFE exome

AF:

0.00582

Gnomad OTH exome

AF:

0.00568

GnomAD4 exome

AF:

0.00596

AC:

8701

AN:

1460096

Hom.:

Cov.:

AF XY:

0.00579

AC XY:

4209

AN XY:

726340

show subpopulations

African (AFR)

AF:

0.000807

AC:

AN:

33478

American (AMR)

AF:

0.00224

AC:

100

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.000842

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.000662

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.0260

AC:

1354

AN:

52094

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00618

AC:

6871

AN:

1111760

Other (OTH)

AF:

0.00442

AC:

267

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

586

1172

1758

2344

2930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.00578

AC:

880

AN:

152250

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

527

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41566

American (AMR)

AF:

0.00307

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000623

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0339

AC:

359

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00593

AC:

403

AN:

68012

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00429

Hom.:

Bravo

AF:

0.00338

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000713

AC:

ESP6500EA

AF:

0.00427

AC:

ExAC

AF:

0.00528

AC:

639

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00507

EpiControl

AF:

0.00439

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZNF407: BS2 -

not specified

Benign:1

Mar 23, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ZNF407-related disorder

Benign:1

Feb 27, 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

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

9.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

REVEL

Benign

0.15

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

0.67

Vest4

0.15

MVP

0.043

MPC

0.19

ClinPred

0.061

GERP RS

3.3

Varity_R

0.13

gMVP

0.57

Mutation Taster

=94/6

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