Genetic Variant ZNF407:p.Leu84Val (chr18-74631269-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_017757.3(ZNF407):c.250C>G(p.Leu84Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.520

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=0.02282989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3 link	c.250C>G	p.Leu84Val	missense_variant	Exon 2 of 9	ENST00000299687.10	NP_060227.2	Q9C0G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF407	ENST00000299687.10 link	c.250C>G	p.Leu84Val	missense_variant	Exon 2 of 9	1	NM_017757.3	ENSP00000299687.4	Q9C0G0-1
ZNF407	ENST00000577538.5 link	c.250C>G	p.Leu84Val	missense_variant	Exon 1 of 7	2		ENSP00000463270.1	Q9C0G0-2
ZNF407	ENST00000309902.10 link	c.250C>G	p.Leu84Val	missense_variant	Exon 1 of 4	2		ENSP00000310359.5	Q9C0G0-3
ZNF407	ENST00000582337.5 link	c.250C>G	p.Leu84Val	missense_variant	Exon 2 of 5	5		ENSP00000462348.1	Q9C0G0-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000722

AC:

AN:

249162

Hom.:

AF XY:

0.0000814

AC XY:

AN XY:

135156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000993

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.250C>G (p.L84V) alteration is located in exon 1 (coding exon 1) of the ZNF407 gene. This alteration results from a C to G substitution at nucleotide position 250, causing the leucine (L) at amino acid position 84 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

0.080

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.34

DANN

Benign

0.88

DEOGEN2

Benign

0.024

.;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.41

.;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.023

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.0

M;M;M;M

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.35

.;N;.;N

REVEL

Benign

0.0070

Sift

Benign

0.082

.;T;.;T

Sift4G

Benign

0.55

T;T;T;T

Polyphen

0.0070

B;B;B;B

Vest4

0.061

MutPred

0.083

Gain of methylation at K85 (P = 0.0322);Gain of methylation at K85 (P = 0.0322);Gain of methylation at K85 (P = 0.0322);Gain of methylation at K85 (P = 0.0322);

MVP

0.18

MPC

0.093

ClinPred

0.026

GERP RS

-1.5

Varity_R

0.054

gMVP

0.095

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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