rs35262183

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_207317.3(ZNF474):ā€‹c.821C>Gā€‹(p.Ser274Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,613,954 control chromosomes in the GnomAD database, including 68,653 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.24 ( 5033 hom., cov: 32)
Exomes š‘“: 0.29 ( 63620 hom. )

Consequence

ZNF474
NM_207317.3 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00
Variant links:
Genes affected
ZNF474 (HGNC:23245): (zinc finger protein 474) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]
ENSG00000250803 (HGNC:53564): (zinc finger protein 475)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0017801821).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF474NM_207317.3 linkuse as main transcriptc.821C>G p.Ser274Cys missense_variant 2/2 ENST00000296600.5 NP_997200.1 Q6S9Z5
ZNF474-AS1XR_007058915.1 linkuse as main transcriptn.271+1813G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF474ENST00000296600.5 linkuse as main transcriptc.821C>G p.Ser274Cys missense_variant 2/21 NM_207317.3 ENSP00000296600.4 Q6S9Z5

Frequencies

GnomAD3 genomes
AF:
0.242
AC:
36749
AN:
151978
Hom.:
5039
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.114
Gnomad AMI
AF:
0.397
Gnomad AMR
AF:
0.218
Gnomad ASJ
AF:
0.332
Gnomad EAS
AF:
0.385
Gnomad SAS
AF:
0.339
Gnomad FIN
AF:
0.334
Gnomad MID
AF:
0.345
Gnomad NFE
AF:
0.286
Gnomad OTH
AF:
0.242
GnomAD3 exomes
AF:
0.287
AC:
72206
AN:
251252
Hom.:
10933
AF XY:
0.296
AC XY:
40139
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.106
Gnomad AMR exome
AF:
0.226
Gnomad ASJ exome
AF:
0.342
Gnomad EAS exome
AF:
0.387
Gnomad SAS exome
AF:
0.346
Gnomad FIN exome
AF:
0.336
Gnomad NFE exome
AF:
0.286
Gnomad OTH exome
AF:
0.282
GnomAD4 exome
AF:
0.291
AC:
424986
AN:
1461858
Hom.:
63620
Cov.:
64
AF XY:
0.294
AC XY:
213972
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.106
Gnomad4 AMR exome
AF:
0.224
Gnomad4 ASJ exome
AF:
0.343
Gnomad4 EAS exome
AF:
0.374
Gnomad4 SAS exome
AF:
0.351
Gnomad4 FIN exome
AF:
0.330
Gnomad4 NFE exome
AF:
0.288
Gnomad4 OTH exome
AF:
0.287
GnomAD4 genome
AF:
0.241
AC:
36729
AN:
152096
Hom.:
5033
Cov.:
32
AF XY:
0.248
AC XY:
18469
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.114
Gnomad4 AMR
AF:
0.218
Gnomad4 ASJ
AF:
0.332
Gnomad4 EAS
AF:
0.385
Gnomad4 SAS
AF:
0.339
Gnomad4 FIN
AF:
0.334
Gnomad4 NFE
AF:
0.285
Gnomad4 OTH
AF:
0.239
Alfa
AF:
0.287
Hom.:
4863
Bravo
AF:
0.227
TwinsUK
AF:
0.285
AC:
1056
ALSPAC
AF:
0.286
AC:
1104
ESP6500AA
AF:
0.116
AC:
512
ESP6500EA
AF:
0.282
AC:
2424
ExAC
AF:
0.286
AC:
34695
Asia WGS
AF:
0.293
AC:
1020
AN:
3478
EpiCase
AF:
0.290
EpiControl
AF:
0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.71
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
12
DANN
Benign
0.91
DEOGEN2
Benign
0.012
T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.32
T
MetaRNN
Benign
0.0018
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.11
Sift
Uncertain
0.025
D
Sift4G
Uncertain
0.021
D
Polyphen
0.98
D
Vest4
0.036
MPC
0.012
ClinPred
0.016
T
GERP RS
2.5
Varity_R
0.093
gMVP
0.090

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: rs35262183; hg19: chr5-121488506; COSMIC: COSV56945671; COSMIC: COSV56945671; API