chr8-144882003-C-G

Variant names:

• chr8-144882003-C-G
• NM_001109689.4:c.1180G>C

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.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. 14/22 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: 0.130
• 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=0.13871169).

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.1180G>C	p.Glu394Gln	missense	Exon 6 of 6	NP_001103159.1	P15622-3
	ZNF250	NM_001363098.2		c.1195G>C	p.Glu399Gln	missense	Exon 6 of 6	NP_001350027.1	P15622-1
	ZNF250	NM_001363099.2		c.1195G>C	p.Glu399Gln	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.1180G>C	p.Glu394Gln	missense	Exon 6 of 6	ENSP00000393442.2	P15622-3
	ZNF250	ENST00000292579.11	TSL:1	c.1195G>C	p.Glu399Gln	missense	Exon 6 of 6	ENSP00000292579.7	P15622-1
	ZNF250	ENST00000940320.1		c.1198G>C	p.Glu400Gln	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	0.094
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
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.68	N
PhyloP100		0.13
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.13	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
Mutation Taster		=93/7	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: chr8-146107388; COSMIC: COSV99481086; COSMIC: COSV99481086;