19-57572750-C-T

Variant summary

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

The NM_017879.3(ZNF416):​c.1154G>A​(p.Gly385Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,614,054 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 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

ZNF416
NM_017879.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.78
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.008362234).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF416NM_017879.3 linkc.1154G>A p.Gly385Asp missense_variant Exon 4 of 4 ENST00000196489.4 NP_060349.1 Q9BWM5
ZNF416NM_001353405.2 linkc.938G>A p.Gly313Asp missense_variant Exon 3 of 3 NP_001340334.1
ZNF416XM_024451594.2 linkc.1094G>A p.Gly365Asp missense_variant Exon 5 of 5 XP_024307362.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF416ENST00000196489.4 linkc.1154G>A p.Gly385Asp missense_variant Exon 4 of 4 1 NM_017879.3 ENSP00000196489.2 Q9BWM5

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000143
AC:
36
AN:
251458
Hom.:
0
AF XY:
0.000162
AC XY:
22
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000828
AC:
121
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.0000976
AC XY:
71
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00287
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000342
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152164
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00143
Alfa
AF:
0.000247
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000824
AC:
10

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 10, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1154G>A (p.G385D) alteration is located in exon 4 (coding exon 4) of the ZNF416 gene. This alteration results from a G to A substitution at nucleotide position 1154, causing the glycine (G) at amino acid position 385 to be replaced by an aspartic acid (D). 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
0.16
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.80
DANN
Uncertain
0.99
DEOGEN2
Benign
0.049
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.051
T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.0084
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.96
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.055
Sift
Benign
0.099
T
Sift4G
Benign
0.085
T
Polyphen
0.50
P
Vest4
0.24
MVP
0.061
MPC
0.31
ClinPred
0.051
T
GERP RS
-3.1
Varity_R
0.035
gMVP
0.024

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: rs201445198; hg19: chr19-58084118; API