Variant chr18-74632619-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017757.3(ZNF407):c.1600G>A(p.Gly534Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02810204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3 linkuse as main transcript	c.1600G>A	p.Gly534Arg	missense_variant	2/9	ENST00000299687.10	NP_060227.2	Q9C0G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF407	ENST00000299687.10 linkuse as main transcript	c.1600G>A	p.Gly534Arg	missense_variant	2/9	1	NM_017757.3	ENSP00000299687.4	Q9C0G0-1
ZNF407	ENST00000577538.5 linkuse as main transcript	c.1600G>A	p.Gly534Arg	missense_variant	1/7	2		ENSP00000463270.1	Q9C0G0-2
ZNF407	ENST00000309902.10 linkuse as main transcript	c.1600G>A	p.Gly534Arg	missense_variant	1/4	2		ENSP00000310359.5	Q9C0G0-3
ZNF407	ENST00000582337.5 linkuse as main transcript	c.1600G>A	p.Gly534Arg	missense_variant	2/5	5		ENSP00000462348.1	Q9C0G0-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000317

AC:

AN:

249196

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00229

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000616

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000635

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000256

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 18, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

.;.;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

.;T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.028

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.0

M;M;M;M

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.4

.;N;.;N

REVEL

Benign

0.23

Sift

Uncertain

0.0010

.;D;.;D

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

0.99

D;D;D;D

Vest4

0.39

MutPred

0.65

Gain of disorder (P = 0.0826);Gain of disorder (P = 0.0826);Gain of disorder (P = 0.0826);Gain of disorder (P = 0.0826);

MVP

0.14

MPC

0.39

ClinPred

0.21

GERP RS

5.9

Varity_R

0.16

gMVP

0.22

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