rs200158544

Positions:

chr18-74631446-G-T

Variant summary

Our verdict is Benign. Variant got -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 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

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=0.002600789).

BP6

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

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3 linkuse as main transcript	c.427G>T	p.Val143Phe	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.427G>T	p.Val143Phe	missense_variant	2/9	1	NM_017757.3	ENSP00000299687	P2	Q9C0G0-1
ZNF407	ENST00000577538.5 linkuse as main transcript	c.427G>T	p.Val143Phe	missense_variant	1/7	2		ENSP00000463270	A2	Q9C0G0-2
ZNF407	ENST00000309902.10 linkuse as main transcript	c.427G>T	p.Val143Phe	missense_variant	1/4	2		ENSP00000310359		Q9C0G0-3
ZNF407	ENST00000582337.5 linkuse as main transcript	c.427G>T	p.Val143Phe	missense_variant	2/5	5		ENSP00000462348		Q9C0G0-3

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

GnomAD3 exomes

AF:

0.00325

AC:

810

AN:

249216

Hom.:

AF XY:

0.00331

AC XY:

448

AN XY:

135206

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 SAS exome

AF:

0.00131

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

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00597

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00154

Gnomad4 FIN exome

AF:

0.00755

Gnomad4 NFE exome

AF:

0.00334

Gnomad4 OTH exome

AF:

0.00303

GnomAD4 genome

AF:

0.00288

AC:

439

AN:

152244

Hom.:

Cov.:

AF XY:

0.00292

AC XY:

217

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00660

Gnomad4 NFE

AF:

0.00410

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00371

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

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	ZNF407: BP4 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 20, 2015

- -

ZNF407-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 2019

This variant is classified as 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

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

.;.;.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.60

.;T;T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0026

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.62

.;N;.;N

REVEL

Benign

0.026

Sift

Uncertain

0.011

.;D;.;D

Sift4G

Uncertain

0.041

D;D;T;T

Polyphen

0.0090

B;B;B;B

Vest4

0.12

MVP

0.068

MPC

0.12

ClinPred

0.0068

GERP RS

2.5

Varity_R

0.072

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