ZNF250 p.Lys369Asn

Variant names:

• chr8-144882076-C-A
• NM_001109689.4:c.1107G>T
• ZNF250 p.Lys369Asn

Your query was ambiguous. Multiple possible variants found:

• chr8-144882076-C-A
• chr8-144882076-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001109689.4(ZNF250):​c.1107G>T​(p.Lys369Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF250 NM_001109689.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18107313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109689.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF250	NM_001109689.4	MANE Select	c.1107G>T	p.Lys369Asn	missense	Exon 6 of 6	NP_001103159.1	P15622-3
	ZNF250	NM_001363098.2		c.1122G>T	p.Lys374Asn	missense	Exon 6 of 6	NP_001350027.1	P15622-1
	ZNF250	NM_001363099.2		c.1122G>T	p.Lys374Asn	missense	Exon 6 of 6	NP_001350028.1	P15622-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF250	ENST00000417550.7	TSL:1 MANE Select	c.1107G>T	p.Lys369Asn	missense	Exon 6 of 6	ENSP00000393442.2	P15622-3
	ZNF250	ENST00000292579.11	TSL:1	c.1122G>T	p.Lys374Asn	missense	Exon 6 of 6	ENSP00000292579.7	P15622-1
	ZNF250	ENST00000940320.1		c.1125G>T	p.Lys375Asn	missense	Exon 6 of 6	ENSP00000610379.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.35
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.076
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.41
gMVP		0.13
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-146107461;