chr8-144882702-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06317261).

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.481T>G	p.Cys161Gly	missense	Exon 6 of 6	NP_001103159.1	P15622-3
	ZNF250	NM_001363098.2		c.496T>G	p.Cys166Gly	missense	Exon 6 of 6	NP_001350027.1	P15622-1
	ZNF250	NM_001363099.2		c.496T>G	p.Cys166Gly	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.481T>G	p.Cys161Gly	missense	Exon 6 of 6	ENSP00000393442.2	P15622-3
	ZNF250	ENST00000292579.11	TSL:1	c.496T>G	p.Cys166Gly	missense	Exon 6 of 6	ENSP00000292579.7	P15622-1
	ZNF250	ENST00000940320.1		c.499T>G	p.Cys167Gly	missense	Exon 6 of 6	ENSP00000610379.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.071	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		-1.4
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.0080
Sift	Benign	0.46	T
Sift4G	Benign	0.51	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
Mutation Taster		=99/1	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

Other links and lift over

hg19: chr8-146108087;