8-144882702-A-C

Variant names:

• chr8-144882702-A-C
• NM_001109689.4:c.481T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001109689.4(ZNF250):​c.481T>G​(p.Cys161Gly) 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. 14/21 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: -1.45

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 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=0.06317261).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF250	NM_001109689.4	c.481T>G	p.Cys161Gly	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.481T>G	p.Cys161Gly	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 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.496T>G (p.C166G) alteration is located in exon 6 (coding exon 5) of the ZNF250 gene. This alteration results from a T to G substitution at nucleotide position 496, causing the cysteine (C) at amino acid position 166 to be replaced by a glycine (G). 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	0.081
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.073
DANN	Benign	0.34
DEOGEN2	Benign	0.064	T;.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.071	T;T;T;T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.063	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Pathogenic	3.2	M;.;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N;N;.;N
REVEL	Benign	0.0080
Sift	Benign	0.46	T;T;.;T
Sift4G	Benign	0.51	T;T;.;T
Polyphen		0.0	B;.;.;.
Vest4		0.065
MutPred		0.27		Loss of stability (P = 0.0377);.;.;.;
MVP		0.15
MPC		0.54
ClinPred		0.12	T
GERP RS		-0.40
Varity_R		0.084
gMVP		0.15

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: chr8-146108087;