Variant rs202203566 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017757.3(ZNF407):c.6077A>G(p.Gln2026Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000993 in 1,609,040 control chromosomes in the GnomAD database, including 3 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 Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

ZNF407
NM_017757.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.139

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:

ZNF407 (HGNC:):

ZNF407 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012239844).

BS2

High Homozygotes in GnomAdExome4 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.6077A>G	p.Gln2026Arg	missense_variant	9/9	ENST00000299687.10	NP_060227.2	Q9C0G0-1
ZNF407	NM_001384475.1 linkuse as main transcript	c.6077A>G	p.Gln2026Arg	missense_variant	9/9		NP_001371404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10 linkuse as main transcript	c.6077A>G	p.Gln2026Arg	missense_variant	9/9	1	NM_017757.3	ENSP00000299687.4		Q9C0G0-1
ZNF407	ENST00000579200.1 linkuse as main transcript	n.2517A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.000790

AC:

120

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00127

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000624

AC:

152

AN:

243740

Hom.:

AF XY:

0.000639

AC XY:

AN XY:

133064

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000639

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000158

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.000670

GnomAD4 exome

AF:

0.00101

AC:

1477

AN:

1456950

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

720

AN XY:

724950

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.000789

AC:

120

AN:

152090

Hom.:

Cov.:

AF XY:

0.000753

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00127

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000895

Hom.:

Bravo

AF:

0.000801

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000957

AC:

ExAC

AF:

0.000620

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.00119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Ambry Genetics	Oct 21, 2021	The c.6077A>G (p.Q2026R) alteration is located in exon 8 (coding exon 8) of the ZNF407 gene. This alteration results from a A to G substitution at nucleotide position 6077, causing the glutamine (Q) at amino acid position 2026 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 09, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.6

DANN

Benign

0.91

DEOGEN2

Benign

0.017

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.38

M_CAP

Benign

0.0095

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.30

REVEL

Benign

0.028

Sift

Benign

0.43

Sift4G

Benign

0.39

Polyphen

0.011

Vest4

0.16

MVP

0.17

MPC

0.20

ClinPred

0.015

GERP RS

0.86

Varity_R

0.060

gMVP

0.13

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