rs773023966

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-144721993-C-A
• chr8-144721993-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18135077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF251	NM_138367.2	c.1667G>T	p.Arg556Leu	missense_variant	Exon 5 of 5	ENST00000292562.12	NP_612376.1
ZNF251	XM_024447324.2	c.1667G>T	p.Arg556Leu	missense_variant	Exon 5 of 5		XP_024303092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF251	ENST00000292562.12	c.1667G>T	p.Arg556Leu	missense_variant	Exon 5 of 5	2	NM_138367.2	ENSP00000292562.7
ZNF251	ENST00000524394.2	n.200-971G>T		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs773023966; hg19: chr8-145947378;