8-144882664-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001109689.4(ZNF250):​c.519G>C​(p.Gln173His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZNF250
NM_001109689.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.154
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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06724784).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF250NM_001109689.4 linkc.519G>C p.Gln173His 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.519G>C p.Gln173His missense_variant Exon 6 of 6 1 NM_001109689.4 ENSP00000393442.2 P15622-3

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152174
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251060
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135692
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000108
AC:
158
AN:
1461708
Hom.:
0
Cov.:
31
AF XY:
0.000110
AC XY:
80
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
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:
0.000130
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152174
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.534G>C (p.Q178H) alteration is located in exon 6 (coding exon 5) of the ZNF250 gene. This alteration results from a G to C substitution at nucleotide position 534, causing the glutamine (Q) at amino acid position 178 to be replaced by a histidine (H). 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
0.090
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
2.0
DANN
Benign
0.82
DEOGEN2
Benign
0.029
T;.;.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.056
N
LIST_S2
Benign
0.068
T;T;T;T
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.067
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.81
L;.;.;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
1.3
N;N;.;N
REVEL
Benign
0.070
Sift
Benign
0.15
T;T;.;T
Sift4G
Benign
0.21
T;T;.;D
Polyphen
0.0010
B;.;.;.
Vest4
0.070
MutPred
0.33
Gain of catalytic residue at L180 (P = 0.0761);.;.;.;
MVP
0.15
MPC
0.41
ClinPred
0.049
T
GERP RS
0.73
Varity_R
0.039
gMVP
0.24

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: rs762257672; hg19: chr8-146108049; API