dbSNP rs776451413: ZNF407:p.Cys483Ser (chr18-74632467-G-C) – 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.1448G>C(p.Cys483Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.836

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=0.037390918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3 link	c.1448G>C	p.Cys483Ser	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.1448G>C	p.Cys483Ser	missense_variant	Exon 2 of 9	1	NM_017757.3	ENSP00000299687.4	Q9C0G0-1
ZNF407	ENST00000577538.5 link	c.1448G>C	p.Cys483Ser	missense_variant	Exon 1 of 7	2		ENSP00000463270.1	Q9C0G0-2
ZNF407	ENST00000309902.10 link	c.1448G>C	p.Cys483Ser	missense_variant	Exon 1 of 4	2		ENSP00000310359.5	Q9C0G0-3
ZNF407	ENST00000582337.5 link	c.1448G>C	p.Cys483Ser	missense_variant	Exon 2 of 5	5		ENSP00000462348.1	Q9C0G0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248986

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135148

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727108

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 02, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.0

DANN

Benign

0.21

DEOGEN2

Benign

0.017

.;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.20

.;T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.037

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.8

N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

1.3

.;N;.;N

REVEL

Benign

0.096

Sift

Benign

1.0

.;T;.;T

Sift4G

Benign

0.81

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.033

MutPred

0.27

Loss of stability (P = 0.0576);Loss of stability (P = 0.0576);Loss of stability (P = 0.0576);Loss of stability (P = 0.0576);

MVP

0.068

MPC

0.10

ClinPred

0.055

GERP RS

2.7

Varity_R

0.060

gMVP

0.18

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