chr8-144882087-C-T

Variant names:

• chr8-144882087-C-T
• rs755313423
• NM_001109689.4:c.1096G>A

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.1096G>A​(p.Glu366Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: ZNF250 NM_001109689.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.919
• Publications: 1 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=0.18658787).

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.1096G>A	p.Glu366Lys	missense	Exon 6 of 6	NP_001103159.1	P15622-3
	ZNF250	NM_001363098.2		c.1111G>A	p.Glu371Lys	missense	Exon 6 of 6	NP_001350027.1	P15622-1
	ZNF250	NM_001363099.2		c.1111G>A	p.Glu371Lys	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.1096G>A	p.Glu366Lys	missense	Exon 6 of 6	ENSP00000393442.2	P15622-3
	ZNF250	ENST00000292579.11	TSL:1	c.1111G>A	p.Glu371Lys	missense	Exon 6 of 6	ENSP00000292579.7	P15622-1
	ZNF250	ENST00000940320.1		c.1114G>A	p.Glu372Lys	missense	Exon 6 of 6	ENSP00000610379.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251436 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727190

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111976

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

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	0.23
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.92
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.12
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.059	T
Polyphen		1.0	D
Vest4		0.23
MutPred		0.62		Gain of methylation at E371 (P = 5e-04)
MVP		0.29
MPC		0.96
ClinPred		0.40	T
GERP RS		3.0
Varity_R		0.40
gMVP		0.28
Mutation Taster		=94/6	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

dbSNP: rs755313423; hg19: chr8-146107472;