8-144881901-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001109689.4(ZNF250):​c.1282G>A​(p.Val428Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ZNF250
NM_001109689.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.505

Publications

1 publications found
Variant links:
Genes affected
ZNF250 (HGNC:13044): (zinc finger protein 250) Enables identical protein binding activity and sequence-specific double-stranded 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: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.026305705).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF250NM_001109689.4 linkc.1282G>A p.Val428Ile missense_variant Exon 6 of 6 ENST00000417550.7 NP_001103159.1 P15622-3B3KNS9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF250ENST00000417550.7 linkc.1282G>A p.Val428Ile missense_variant Exon 6 of 6 1 NM_001109689.4 ENSP00000393442.2 P15622-3

Frequencies

GnomAD3 genomes
AF:
0.0000333
AC:
5
AN:
150192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000995
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000557
AC:
14
AN:
251454
AF XY:
0.0000441
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000761
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
727248
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.000428
AC:
17
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000450
AC:
5
AN:
1112012
Other (OTH)
AF:
0.0000828
AC:
5
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000333
AC:
5
AN:
150320
Hom.:
0
Cov.:
33
AF XY:
0.0000272
AC XY:
2
AN XY:
73458
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
40848
American (AMR)
AF:
0.00
AC:
0
AN:
15118
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3454
East Asian (EAS)
AF:
0.000997
AC:
5
AN:
5016
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4692
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10416
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
272
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67506
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.515
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000540
Hom.:
0
Bravo
AF:
0.0000302
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 16, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1297G>A (p.V433I) alteration is located in exon 6 (coding exon 5) of the ZNF250 gene. This alteration results from a G to A substitution at nucleotide position 1297, causing the valine (V) at amino acid position 433 to be replaced by an isoleucine (I). 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
0.13
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.056
T;.
Eigen
Benign
-0.071
Eigen_PC
Benign
-0.060
FATHMM_MKL
Benign
0.065
N
LIST_S2
Benign
0.15
T;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.026
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.30
N;.
PhyloP100
-0.51
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.33
N;N
REVEL
Benign
0.060
Sift
Benign
0.26
T;T
Sift4G
Benign
0.46
T;T
Polyphen
0.98
D;.
Vest4
0.14
MVP
0.28
MPC
0.95
ClinPred
0.13
T
GERP RS
4.1
Varity_R
0.048
gMVP
0.054
Mutation Taster
=95/5
polymorphism

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: rs368254797; hg19: chr8-146107286; COSMIC: COSV52968713; COSMIC: COSV52968713; API