NM_138367.2:c.1667G>T

Variant names:

• chr8-144721993-C-A
• rs773023966
• NM_138367.2:c.1667G>T

Variant summary

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

The NM_138367.2(ZNF251):​c.1667G>T​(p.Arg556Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R556H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF251 NM_138367.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

ZNF251 (HGNC:13045): (zinc finger protein 251) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within hematopoietic stem cell homeostasis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290885 (HGNC:):

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=0.18135077).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138367.2. 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
	ZNF251	NM_138367.2	MANE Select	c.1667G>T	p.Arg556Leu	missense	Exon 5 of 5	NP_612376.1	Q9BRH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF251	ENST00000292562.12	TSL:2 MANE Select	c.1667G>T	p.Arg556Leu	missense	Exon 5 of 5	ENSP00000292562.7	Q9BRH9
	ZNF251	ENST00000861866.1		c.1667G>T	p.Arg556Leu	missense	Exon 4 of 4	ENSP00000531925.1
	ZNF251	ENST00000861867.1		c.1667G>T	p.Arg556Leu	missense	Exon 5 of 5	ENSP00000531926.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.51	N
PhyloP100		1.1
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.040
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.0050	B
Vest4		0.17
MutPred		0.62		Loss of MoRF binding (P = 6e-04)
MVP		0.17
MPC		0.18
ClinPred		0.32	T
GERP RS		1.0
Varity_R		0.090
gMVP		0.17
Mutation Taster		=96/4	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: rs773023966; hg19: chr8-145947378;