rs200073088

Positions:

chr18-74877258-A-G

Variant summary

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

The NM_017757.3(ZNF407):c.4939A>G(p.Met1647Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000787 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 4.95

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 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=0.05272156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF407	NM_017757.3 linkuse as main transcript	c.4939A>G	p.Met1647Val	missense_variant	5/9	ENST00000299687.10	NP_060227.2
ZNF407	NM_001384475.1 linkuse as main transcript	c.4939A>G	p.Met1647Val	missense_variant	5/9		NP_001371404.1
ZNF407	NM_001146189.1 linkuse as main transcript	c.4939A>G	p.Met1647Val	missense_variant	4/7		NP_001139661.1
ZNF407	XM_017025838.3 linkuse as main transcript	c.4939A>G	p.Met1647Val	missense_variant	5/8		XP_016881327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10 linkuse as main transcript	c.4939A>G	p.Met1647Val	missense_variant	5/9	1	NM_017757.3	ENSP00000299687	P2	Q9C0G0-1
ZNF407	ENST00000577538.5 linkuse as main transcript	c.4939A>G	p.Met1647Val	missense_variant	4/7	2		ENSP00000463270	A2	Q9C0G0-2
ZNF407	ENST00000581829.2 linkuse as main transcript	c.55A>G	p.Met19Val	missense_variant	1/4	5		ENSP00000479246
ZNF407	ENST00000584235.5 linkuse as main transcript	c.61A>G	p.Met21Val	missense_variant	1/4	3		ENSP00000481798

Frequencies

GnomAD3 genomes

AF:

0.000433

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000802

AC:

AN:

249262

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.0000290

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:

0.0000417

AC:

AN:

1461656

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.0000671

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:

0.0000663

GnomAD4 genome

AF:

0.000433

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.0000653

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:

0.000125

Hom.:

Bravo

AF:

0.000487

ESP6500AA

AF:

0.000775

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000828

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 21, 2014	- -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2022

The c.4939A>G (p.M1647V) alteration is located in exon 4 (coding exon 4) of the ZNF407 gene. This alteration results from a A to G substitution at nucleotide position 4939, causing the methionine (M) at amino acid position 1647 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.042

.;T;.

Eigen

Benign

-0.097

Eigen_PC

Benign

0.060

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

0.75

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.87

.;N;.

REVEL

Benign

0.085

Sift

Benign

0.068

.;T;.

Sift4G

Benign

0.090

T;T;T

Polyphen

0.023

B;B;.

Vest4

0.32

MVP

0.23

MPC

0.41

ClinPred

0.070

GERP RS

3.4

Varity_R

0.13

gMVP

0.77

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