Genetic Variant ZNF251:p.Gly544Ser (chr8-144722030-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_138367.2(ZNF251):c.1630G>A(p.Gly544Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,610,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF251
NM_138367.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.21

Publications

0 publications found

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]

ZNF251 links:

ENSG00000290885 (HGNC:):

ENSG00000290885 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060373485).

BP6

Variant 8-144722030-C-T is Benign according to our data. Variant chr8-144722030-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3474841.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1630G>A	p.Gly544Ser	missense	Exon 5 of 5	NP_612376.1	Q9BRH9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF251	ENST00000292562.12	TSL:2 MANE Select	c.1630G>A	p.Gly544Ser	missense	Exon 5 of 5	ENSP00000292562.7	Q9BRH9
ZNF251	ENST00000861866.1		c.1630G>A	p.Gly544Ser	missense	Exon 4 of 4	ENSP00000531925.1
ZNF251	ENST00000861867.1		c.1630G>A	p.Gly544Ser	missense	Exon 5 of 5	ENSP00000531926.1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000244

AC:

AN:

246260

AF XY:

0.0000225

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1457822

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724880

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33430

American (AMR)

AF:

0.000361

AC:

AN:

44380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25760

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53252

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1109852

Other (OTH)

AF:

0.0000665

AC:

AN:

60184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41552

American (AMR)

AF:

0.000327

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.2

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.19

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.0022

M_CAP

Benign

0.0018

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

-2.2

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.077

Sift

Benign

0.12

Sift4G

Uncertain

0.032

Polyphen

0.0030

Vest4

0.065

MVP

0.067

MPC

0.14

ClinPred

0.044

GERP RS

-0.91

Varity_R

0.058

gMVP

0.13

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over