19-57573337-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_017879.3(ZNF416):​c.567G>A​(p.Pro189Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000894 in 1,614,246 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00093 ( 1 hom. )

Consequence

ZNF416
NM_017879.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.17
Variant links:
Genes affected
ZNF416 (HGNC:20645): (zinc finger protein 416) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within cardiac muscle hypertrophy; negative regulation of cell growth involved in cardiac muscle cell development; and negative regulation of protein phosphorylation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 19-57573337-C-T is Benign according to our data. Variant chr19-57573337-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650574.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.17 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF416NM_017879.3 linkc.567G>A p.Pro189Pro synonymous_variant Exon 4 of 4 ENST00000196489.4 NP_060349.1 Q9BWM5
ZNF416NM_001353405.2 linkc.351G>A p.Pro117Pro synonymous_variant Exon 3 of 3 NP_001340334.1
ZNF416XM_024451594.2 linkc.507G>A p.Pro169Pro synonymous_variant Exon 5 of 5 XP_024307362.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF416ENST00000196489.4 linkc.567G>A p.Pro189Pro synonymous_variant Exon 4 of 4 1 NM_017879.3 ENSP00000196489.2 Q9BWM5

Frequencies

GnomAD3 genomes
AF:
0.000512
AC:
78
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000753
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000897
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000593
AC:
149
AN:
251332
Hom.:
0
AF XY:
0.000648
AC XY:
88
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000621
Gnomad FIN exome
AF:
0.000739
Gnomad NFE exome
AF:
0.000941
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000934
AC:
1365
AN:
1461892
Hom.:
1
Cov.:
31
AF XY:
0.000901
AC XY:
655
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000893
Gnomad4 FIN exome
AF:
0.000655
Gnomad4 NFE exome
AF:
0.00108
Gnomad4 OTH exome
AF:
0.000745
GnomAD4 genome
AF:
0.000512
AC:
78
AN:
152354
Hom.:
0
Cov.:
33
AF XY:
0.000537
AC XY:
40
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.000753
Gnomad4 NFE
AF:
0.000897
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000621
Hom.:
0
Bravo
AF:
0.000419
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00120
EpiControl
AF:
0.00130

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ZNF416: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
2.6
DANN
Benign
0.58

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: rs141508737; hg19: chr19-58084705; COSMIC: COSV52185300; API