Variant rs74861823 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000299687.10(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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

ZNF407
ENST00000299687.10 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.503

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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 [Likely_benign]. Clinvar id is 437370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3 linkuse as main transcript	c.490A>G	p.Arg164Gly	missense_variant	2/9	ENST00000299687.10	NP_060227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10 linkuse as main transcript	c.490A>G	p.Arg164Gly	missense_variant	2/9	1	NM_017757.3	ENSP00000299687	P2	Q9C0G0-1
ZNF407	ENST00000577538.5 linkuse as main transcript	c.490A>G	p.Arg164Gly	missense_variant	1/7	2		ENSP00000463270	A2	Q9C0G0-2
ZNF407	ENST00000309902.10 linkuse as main transcript	c.490A>G	p.Arg164Gly	missense_variant	1/4	2		ENSP00000310359		Q9C0G0-3
ZNF407	ENST00000582337.5 linkuse as main transcript	c.490A>G	p.Arg164Gly	missense_variant	2/5	5		ENSP00000462348		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

GnomAD3 exomes

AF:

0.000759

AC:

189

AN:

249168

Hom.:

AF XY:

0.000577

AC XY:

AN XY:

135182

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 SAS 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

Gnomad4 AFR exome

AF:

0.00911

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.00287

AC:

437

AN:

152346

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00986

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00102

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2018	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 19, 2017

- -

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

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

MutationTaster

Benign

1.0

N;N;N;N

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

Varity_R

0.077

gMVP

0.12

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