NM_017757.3:c.427G>T

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.427G>T(p.Val143Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,613,954 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 10 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.450

Publications

10 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002600789).

BP6

Variant 18-74631446-G-T is Benign according to our data. Variant chr18-74631446-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 130822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017757.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF407	NM_017757.3	MANE Select	c.427G>T	p.Val143Phe	missense	Exon 2 of 9	NP_060227.2	Q9C0G0-1
ZNF407	NM_001384475.1		c.427G>T	p.Val143Phe	missense	Exon 2 of 9	NP_001371404.1	Q9C0G0-1
ZNF407	NM_001146189.1		c.427G>T	p.Val143Phe	missense	Exon 1 of 7	NP_001139661.1	Q9C0G0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF407	ENST00000299687.10	TSL:1 MANE Select	c.427G>T	p.Val143Phe	missense	Exon 2 of 9	ENSP00000299687.4	Q9C0G0-1
ZNF407	ENST00000577538.5	TSL:2	c.427G>T	p.Val143Phe	missense	Exon 1 of 7	ENSP00000463270.1	Q9C0G0-2
ZNF407	ENST00000949102.1		c.427G>T	p.Val143Phe	missense	Exon 2 of 9	ENSP00000619161.1

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

439

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00660

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00410

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00325

AC:

810

AN:

249216

AF XY:

0.00331

show subpopulations

Gnomad AFR exome

AF:

0.000581

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00577

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00729

Gnomad NFE exome

AF:

0.00432

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00320

AC:

4681

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

2310

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33480

American (AMR)

AF:

0.00127

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00597

AC:

156

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00154

AC:

133

AN:

86258

European-Finnish (FIN)

AF:

0.00755

AC:

403

AN:

53400

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00334

AC:

3712

AN:

1111870

Other (OTH)

AF:

0.00303

AC:

183

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

296

591

887

1182

1478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

248

372

496

620

<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:

0.00288

AC:

439

AN:

152244

Hom.:

Cov.:

AF XY:

0.00292

AC XY:

217

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41546

American (AMR)

AF:

0.00163

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00187

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00660

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00410

AC:

279

AN:

68010

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

107

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:

0.00342

Hom.:

Bravo

AF:

0.00249

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000796

AC:

ESP6500EA

AF:

0.00438

AC:

ExAC

AF:

0.00298

AC:

360

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00385

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

ZNF407-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.60

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

PhyloP100

0.45

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.62

REVEL

Benign

0.026

Sift

Uncertain

0.011

Sift4G

Uncertain

0.041

Polyphen

0.0090

Vest4

0.12

MVP

0.068

MPC

0.12

ClinPred

0.0068

GERP RS

2.5

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.072

gMVP

0.12

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over