Genetic Variant NM_003446.4:c.785C>T (chrX-47412858-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003446.4(ZNF157):c.785C>T(p.Thr262Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,209,533 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000025 ( 0 hom. 11 hem. )

Consequence

ZNF157
NM_003446.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05815971).

BP6

Variant X-47412858-C-T is Benign according to our data. Variant chrX-47412858-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3474353.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 11 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.785C>T	p.Thr262Met	missense	Exon 4 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.785C>T	p.Thr262Met	missense	Exon 4 of 4	ENSP00000366273.4	P51786

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000548

AC:

AN:

182566

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1097887

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

363259

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26395

American (AMR)

AF:

0.00

AC:

AN:

35189

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19366

East Asian (EAS)

AF:

0.00

AC:

AN:

30198

South Asian (SAS)

AF:

0.0000370

AC:

AN:

54098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

841901

Other (OTH)

AF:

0.00

AC:

AN:

46086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.0000269

AC:

AN:

111646

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33912

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30665

American (AMR)

AF:

0.00

AC:

AN:

10489

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3578

South Asian (SAS)

AF:

0.00

AC:

AN:

2706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53114

Other (OTH)

AF:

0.00

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00000824

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

0.17

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.1

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.033

FATHMM_MKL

Benign

0.000010

LIST_S2

Benign

0.15

M_CAP

Benign

0.025

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

PhyloP100

-1.6

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.3

REVEL

Benign

0.015

Sift

Benign

0.17

Sift4G

Benign

0.13

Polyphen

0.047

Vest4

0.090

MVP

0.34

MPC

0.029

ClinPred

0.079

GERP RS

1.2

Varity_R

0.033

gMVP

0.044

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