8-144882003-C-G

Position:

• chr8-144882003-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001109689.4(ZNF250):​c.1180G>C​(p.Glu394Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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: 0.130

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13871169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF250	NM_001109689.4	c.1180G>C	p.Glu394Gln	missense_variant	6/6	ENST00000417550.7	NP_001103159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF250	ENST00000417550.7	c.1180G>C	p.Glu394Gln	missense_variant	6/6	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2024

The c.1195G>C (p.E399Q) 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 1195, causing the glutamic acid (E) at amino acid position 399 to be replaced by a glutamine (Q). 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	0.094
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.090
Eigen_PC	Benign	-0.090
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.68	N;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.99	D;.
Vest4		0.11
MutPred		0.45		Loss of ubiquitination at K402 (P = 0.0415);.;
MVP		0.30
MPC		0.69
ClinPred		0.84	D
GERP RS		4.1
Varity_R		0.33
gMVP		0.12

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: chr8-146107388; COSMIC: COSV99481086; COSMIC: COSV99481086;