16-49635950-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001379286.1(ZNF423):​c.3226C>A​(p.Leu1076Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000663 in 1,595,168 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 5 hom., cov: 33)
Exomes 𝑓: 0.00034 ( 7 hom. )

Consequence

ZNF423
NM_001379286.1 missense

Scores

4
14

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.50
Variant links:
Genes affected
ZNF423 (HGNC:16762): (zinc finger protein 423) The protein encoded by this gene is a nuclear protein that belongs to the family of Kruppel-like C2H2 zinc finger proteins. It functions as a DNA-binding transcription factor by using distinct zinc fingers in different signaling pathways. Thus, it is thought that this gene may have multiple roles in signal transduction during development. Mutations in this gene are associated with nephronophthisis-14 and Joubert syndrome-19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009529829).
BP6
Variant 16-49635950-G-T is Benign according to our data. Variant chr16-49635950-G-T is described in ClinVar as [Benign]. Clinvar id is 260533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-49635950-G-T is described in Lovd as [Benign].
BS2
High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF423NM_001379286.1 linkc.3226C>A p.Leu1076Met missense_variant Exon 4 of 8 ENST00000563137.7 NP_001366215.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF423ENST00000563137.7 linkc.3226C>A p.Leu1076Met missense_variant Exon 4 of 8 5 NM_001379286.1 ENSP00000455588.3 A0A7P0Q1F0

Frequencies

GnomAD3 genomes
AF:
0.00372
AC:
566
AN:
152218
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0132
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
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:
0.0000588
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000956
AC:
225
AN:
235450
Hom.:
1
AF XY:
0.000505
AC XY:
64
AN XY:
126856
show subpopulations
Gnomad AFR exome
AF:
0.0133
Gnomad AMR exome
AF:
0.000239
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:
0.0000188
Gnomad OTH exome
AF:
0.000698
GnomAD4 exome
AF:
0.000342
AC:
494
AN:
1442832
Hom.:
7
Cov.:
31
AF XY:
0.000253
AC XY:
181
AN XY:
715138
show subpopulations
Gnomad4 AFR exome
AF:
0.0132
Gnomad4 AMR exome
AF:
0.000298
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:
0.00000908
Gnomad4 OTH exome
AF:
0.000504
GnomAD4 genome
AF:
0.00370
AC:
563
AN:
152336
Hom.:
5
Cov.:
33
AF XY:
0.00360
AC XY:
268
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0131
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000680
Hom.:
5
Bravo
AF:
0.00397
ESP6500AA
AF:
0.0148
AC:
65
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00129
AC:
156
Asia WGS
AF:
0.000866
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Nephronophthisis 14 Benign:2
Jan 14, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Dec 05, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Oct 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ZNF423: BS1, BS2 -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.084
T;.;.;T;.;.;.
Eigen
Benign
0.12
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.90
.;.;.;D;.;D;D
MetaRNN
Benign
0.0095
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.;.;N;.;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.27
N;N;N;N;N;N;N
REVEL
Benign
0.10
Sift
Benign
0.20
T;T;T;T;T;T;T
Sift4G
Benign
0.17
T;T;T;T;T;T;T
Polyphen
0.62
P;.;.;P;.;.;.
Vest4
0.38
MVP
0.068
MPC
0.86
ClinPred
0.030
T
GERP RS
4.2
Varity_R
0.069
gMVP
0.15

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.

Other links and lift over

dbSNP: rs79706004; hg19: chr16-49669861; API