19-56574646-A-G

Variant summary

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

The NM_001001668.4(ZNF470):ā€‹c.196A>Gā€‹(p.Ile66Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,040 control chromosomes in the GnomAD database, including 2 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000017 ( 2 hom. )

Consequence

ZNF470
NM_001001668.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.728
Variant links:
Genes affected
ZNF470 (HGNC:22220): (zinc finger protein 470) 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. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

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=0.016316265).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF470NM_001001668.4 linkuse as main transcriptc.196A>G p.Ile66Val missense_variant 5/6 ENST00000330619.13 NP_001001668.3
ZNF470XM_047438804.1 linkuse as main transcriptc.196A>G p.Ile66Val missense_variant 6/7 XP_047294760.1
ZNF470XM_047438805.1 linkuse as main transcriptc.43A>G p.Ile15Val missense_variant 4/5 XP_047294761.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF470ENST00000330619.13 linkuse as main transcriptc.196A>G p.Ile66Val missense_variant 5/61 NM_001001668.4 ENSP00000333223 P1Q6ECI4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000599
AC:
15
AN:
250476
Hom.:
1
AF XY:
0.0000960
AC XY:
13
AN XY:
135442
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000327
Gnomad SAS exome
AF:
0.000295
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461040
Hom.:
2
Cov.:
32
AF XY:
0.0000275
AC XY:
20
AN XY:
726832
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000189
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 05, 2023The c.196A>G (p.I66V) alteration is located in exon 5 (coding exon 3) of the ZNF470 gene. This alteration results from a A to G substitution at nucleotide position 196, causing the isoleucine (I) at amino acid position 66 to be replaced by a valine (V). 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
0.077
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
3.1
DANN
Benign
0.22
DEOGEN2
Benign
0.00014
T;.;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.13
.;T;T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.016
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.56
N;.;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.010
N;.;N
REVEL
Benign
0.014
Sift
Benign
1.0
T;.;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;.;B
Vest4
0.075
MutPred
0.36
Gain of ubiquitination at K68 (P = 0.0872);Gain of ubiquitination at K68 (P = 0.0872);Gain of ubiquitination at K68 (P = 0.0872);
MVP
0.12
MPC
0.013
ClinPred
0.019
T
GERP RS
-1.8
Varity_R
0.050
gMVP
0.022

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: rs753179426; hg19: chr19-57086015; API