chr22-23743958-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021916.4(ZNF70):​c.1183G>A​(p.Glu395Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF70
NM_021916.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.938
Variant links:
Genes affected
ZNF70 (HGNC:13140): (zinc finger protein 70) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33054906).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF70NM_021916.4 linkc.1183G>A p.Glu395Lys missense_variant Exon 2 of 2 ENST00000341976.5 NP_068735.1 Q9UC06B3KV76

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF70ENST00000341976.5 linkc.1183G>A p.Glu395Lys missense_variant Exon 2 of 2 1 NM_021916.4 ENSP00000339314.3 Q9UC06

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461854
Hom.:
0
Cov.:
34
AF XY:
0.00000413
AC XY:
3
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1183G>A (p.E395K) alteration is located in exon 2 (coding exon 1) of the ZNF70 gene. This alteration results from a G to A substitution at nucleotide position 1183, causing the glutamic acid (E) at amino acid position 395 to be replaced by a lysine (K). 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
0.21
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
22
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.23
T
Eigen
Benign
0.12
Eigen_PC
Benign
0.037
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.19
T
M_CAP
Benign
0.055
D
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.096
Sift
Benign
0.051
T
Sift4G
Benign
0.066
T
Polyphen
1.0
D
Vest4
0.42
MVP
0.067
MPC
0.61
ClinPred
0.82
D
GERP RS
3.2
Varity_R
0.15
gMVP
0.059

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: rs368119563; hg19: chr22-24086145; API