chr10-43616797-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145312.4(ZNF485):​c.754G>A​(p.Ala252Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,688 control chromosomes in the GnomAD database, including 42,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.22 ( 4025 hom., cov: 33)
Exomes 𝑓: 0.22 ( 38137 hom. )

Consequence

ZNF485
NM_145312.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.448

Publications

24 publications found
Variant links:
Genes affected
ZNF485 (HGNC:23440): (zinc finger protein 485) Predicted to enable DNA-binding transcription activator 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 be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0046267807).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF485NM_145312.4 linkc.754G>A p.Ala252Thr missense_variant Exon 5 of 5 ENST00000361807.8 NP_660355.2 Q8NCK3-1A0A024R7T5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF485ENST00000361807.8 linkc.754G>A p.Ala252Thr missense_variant Exon 5 of 5 1 NM_145312.4 ENSP00000354694.3 Q8NCK3-1
ZNF485ENST00000374435.3 linkc.754G>A p.Ala252Thr missense_variant Exon 5 of 5 1 ENSP00000363558.3 Q8NCK3-1

Frequencies

GnomAD3 genomes
AF:
0.224
AC:
34089
AN:
151846
Hom.:
4023
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.273
Gnomad AMI
AF:
0.154
Gnomad AMR
AF:
0.202
Gnomad ASJ
AF:
0.209
Gnomad EAS
AF:
0.00214
Gnomad SAS
AF:
0.186
Gnomad FIN
AF:
0.150
Gnomad MID
AF:
0.146
Gnomad NFE
AF:
0.234
Gnomad OTH
AF:
0.224
GnomAD2 exomes
AF:
0.193
AC:
48508
AN:
251072
AF XY:
0.193
show subpopulations
Gnomad AFR exome
AF:
0.270
Gnomad AMR exome
AF:
0.157
Gnomad ASJ exome
AF:
0.210
Gnomad EAS exome
AF:
0.000925
Gnomad FIN exome
AF:
0.165
Gnomad NFE exome
AF:
0.229
Gnomad OTH exome
AF:
0.207
GnomAD4 exome
AF:
0.223
AC:
325407
AN:
1461726
Hom.:
38137
Cov.:
38
AF XY:
0.222
AC XY:
161147
AN XY:
727156
show subpopulations
African (AFR)
AF:
0.269
AC:
9017
AN:
33478
American (AMR)
AF:
0.164
AC:
7348
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.214
AC:
5601
AN:
26134
East Asian (EAS)
AF:
0.000655
AC:
26
AN:
39694
South Asian (SAS)
AF:
0.186
AC:
16039
AN:
86254
European-Finnish (FIN)
AF:
0.164
AC:
8751
AN:
53352
Middle Eastern (MID)
AF:
0.178
AC:
1026
AN:
5768
European-Non Finnish (NFE)
AF:
0.238
AC:
264467
AN:
1111942
Other (OTH)
AF:
0.217
AC:
13132
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.472
Heterozygous variant carriers
0
15096
30191
45287
60382
75478
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
8938
17876
26814
35752
44690
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.224
AC:
34110
AN:
151962
Hom.:
4025
Cov.:
33
AF XY:
0.217
AC XY:
16123
AN XY:
74280
show subpopulations
African (AFR)
AF:
0.273
AC:
11296
AN:
41448
American (AMR)
AF:
0.201
AC:
3075
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.209
AC:
725
AN:
3470
East Asian (EAS)
AF:
0.00214
AC:
11
AN:
5138
South Asian (SAS)
AF:
0.187
AC:
898
AN:
4810
European-Finnish (FIN)
AF:
0.150
AC:
1582
AN:
10566
Middle Eastern (MID)
AF:
0.140
AC:
41
AN:
292
European-Non Finnish (NFE)
AF:
0.234
AC:
15873
AN:
67936
Other (OTH)
AF:
0.222
AC:
469
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
1354
2707
4061
5414
6768
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
348
696
1044
1392
1740
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.226
Hom.:
13854
Bravo
AF:
0.228
TwinsUK
AF:
0.240
AC:
890
ALSPAC
AF:
0.234
AC:
900
ESP6500AA
AF:
0.268
AC:
1183
ESP6500EA
AF:
0.232
AC:
1995
ExAC
AF:
0.196
AC:
23788
Asia WGS
AF:
0.0920
AC:
321
AN:
3478
EpiCase
AF:
0.230
EpiControl
AF:
0.222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.85
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
12
DANN
Benign
0.67
DEOGEN2
Benign
0.0044
T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.00023
N
LIST_S2
Benign
0.16
.;T
MetaRNN
Benign
0.0046
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-0.95
N;N
PhyloP100
0.45
PrimateAI
Benign
0.37
T
PROVEAN
Benign
0.29
N;N
REVEL
Benign
0.012
Sift
Benign
0.61
T;T
Sift4G
Benign
0.29
T;T
Polyphen
0.0010
B;B
Vest4
0.018
MPC
0.12
ClinPred
0.00018
T
GERP RS
0.50
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.065
gMVP
0.012
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12354886; hg19: chr10-44112245; COSMIC: COSV62425571; COSMIC: COSV62425571; API