chr8-144882724-A-T

Position:

• chr8-144882724-A-T

Variant summary

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

The NM_001109689.4(ZNF250):​c.459T>A​(p.Asn153Lys) 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. 15/21 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: -0.642

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=0.045013785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF250	NM_001109689.4	c.459T>A	p.Asn153Lys	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.459T>A	p.Asn153Lys	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

Aug 15, 2023

The c.474T>A (p.N158K) alteration is located in exon 6 (coding exon 5) of the ZNF250 gene. This alteration results from a T to A substitution at nucleotide position 474, causing the asparagine (N) at amino acid position 158 to be replaced by a lysine (K). 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	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.7
DANN	Benign	0.19
DEOGEN2	Benign	0.017	T;.;.;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.17	T;T;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.045	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.090	N;.;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.72	N;N;.;N
REVEL	Benign	0.020
Sift	Benign	0.44	T;T;.;T
Sift4G	Benign	0.53	T;T;.;T
Polyphen		0.029	B;.;.;.
Vest4		0.13
MutPred		0.44		Gain of ubiquitination at N158 (P = 0.0051);.;.;.;
MVP		0.18
MPC		0.51
ClinPred		0.042	T
GERP RS		1.4
Varity_R		0.10
gMVP		0.053

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: chr8-146108109;