Genetic Variant ZNF157:p.Pro46Arg (chrX-47410340-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003446.4(ZNF157):c.137C>G(p.Pro46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,209,504 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000020 ( 0 hom. 5 hem. )

Consequence

ZNF157
NM_003446.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.141

Publications

0 publications found

Variant links:

Genes affected

ZNF157 (HGNC:12942): (zinc finger protein 157) This gene product is a likely zinc finger family transcription factor. It contains KRAB-A and KRAB-B domains that act as transcriptional repressors in related proteins, and multiple zinc finger DNA binding motifs and finger linking regions characteristic of the Kruppel family. This gene is part of a gene cluster on chromosome Xp11.23. [provided by RefSeq, Jul 2008]

ZNF157 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=0.07545823).

BS2

High Hemizygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003446.4. 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
	ZNF157	NM_003446.4	MANE Select	c.137C>G	p.Pro46Arg	missense	Exon 2 of 4	NP_003437.2	P51786

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF157	ENST00000377073.4	TSL:1 MANE Select	c.137C>G	p.Pro46Arg	missense	Exon 2 of 4	ENSP00000366273.4	P51786

Frequencies

GnomAD3 genomes

AF:

0.000144

AC:

AN:

111462

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000378

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000654

AC:

AN:

183416

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.000109

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:

0.0000200

AC:

AN:

1098042

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363400

show subpopulations

African (AFR)

AF:

0.000644

AC:

AN:

26399

American (AMR)

AF:

0.0000852

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54145

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841952

Other (OTH)

AF:

0.0000434

AC:

AN:

46090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000144

AC:

AN:

111462

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

33620

show subpopulations

African (AFR)

AF:

0.000490

AC:

AN:

30637

American (AMR)

AF:

0.00

AC:

AN:

10369

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.000378

AC:

AN:

2646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6037

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53133

Other (OTH)

AF:

0.00

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.0000712

Hom.:

Bravo

AF:

0.000246

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.12

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.074

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.33

M_CAP

Benign

0.0031

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

0.14

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.088

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

0.37

Vest4

0.22

MVP

0.50

MPC

0.087

ClinPred

0.13

GERP RS

-3.0

Varity_R

0.68

gMVP

0.47

Mutation Taster

=100/0

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

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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