8-144882596-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001109689.4(ZNF250):​c.587G>A​(p.Cys196Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF250
NM_001109689.4 missense

Scores

9
5
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.01
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF250NM_001109689.4 linkc.587G>A p.Cys196Tyr 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.587G>A p.Cys196Tyr missense_variant Exon 6 of 6 1 NM_001109689.4 ENSP00000393442.2 P15622-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.602G>A (p.C201Y) 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 602, causing the cysteine (C) at amino acid position 201 to be replaced by a tyrosine (Y). 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T;.
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.025
D
MetaRNN
Pathogenic
0.93
D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Pathogenic
3.0
M;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-10
D;D
REVEL
Uncertain
0.55
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
D;.
Vest4
0.66
MutPred
0.75
Gain of phosphorylation at C201 (P = 0.0374);.;
MVP
0.77
MPC
1.7
ClinPred
1.0
D
GERP RS
3.9
Varity_R
0.95
gMVP
0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-146107981; API