rs773023966

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12
Variant links:
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]

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ACMG classification

Classification made for transcript

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
ZNF251NM_138367.2 linkc.1667G>T p.Arg556Leu missense_variant Exon 5 of 5 ENST00000292562.12 NP_612376.1 Q9BRH9
ZNF251XM_024447324.2 linkc.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
ZNF251ENST00000292562.12 linkc.1667G>T p.Arg556Leu missense_variant Exon 5 of 5 2 NM_138367.2 ENSP00000292562.7 Q9BRH9
ZNF251ENST00000524394.2 linkn.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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs773023966; hg19: chr8-145947378; API