8-144882596-C-T

Variant names:

• chr8-144882596-C-T
• NM_001109689.4:c.587G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.01

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]

ACMG classification

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
ZNF250	NM_001109689.4	c.587G>A	p.Cys196Tyr	missense_variant	Exon 6 of 6	ENST00000417550.7	NP_001103159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF250	ENST00000417550.7	c.587G>A	p.Cys196Tyr	missense_variant	Exon 6 of 6	1	NM_001109689.4	ENSP00000393442.2

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

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;