dbSNP rs782495626: ZFP92:p.Ala381Val (chrX-153421519-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001136273.2(ZFP92):c.1142C>T(p.Ala381Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,135,354 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 102 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., 7 hem., cov: 26)

Exomes 𝑓: 0.00024 ( 0 hom. 95 hem. )

Consequence

ZFP92
NM_001136273.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.545

Publications

0 publications found

Variant links:

Genes affected

ZFP92 (HGNC:12865): (ZFP92 zinc finger protein) 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 be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFP92 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066350102).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136273.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP92	NM_001136273.2	MANE Select	c.1142C>T	p.Ala381Val	missense	Exon 6 of 6	NP_001129745.1	A6NM28
ZFP92	NM_001386944.1		c.1142C>T	p.Ala381Val	missense	Exon 5 of 5	NP_001373873.1	A6NM28
ZFP92	NM_001386945.1		c.1142C>T	p.Ala381Val	missense	Exon 7 of 7	NP_001373874.1	A6NM28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP92	ENST00000338647.7	TSL:5 MANE Select	c.1142C>T	p.Ala381Val	missense	Exon 6 of 6	ENSP00000462054.1	A6NM28
	ZFP92	ENST00000881745.1		c.1142C>T	p.Ala381Val	missense	Exon 5 of 5	ENSP00000551804.1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

113449

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000955

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000734

Gnomad ASJ

AF:

0.000752

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000413

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000306

AC:

AN:

78365

AF XY:

0.000280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00212

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000304

Gnomad OTH exome

AF:

0.00161

GnomAD4 exome

AF:

0.000237

AC:

242

AN:

1021859

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

329253

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22917

American (AMR)

AF:

0.000194

AC:

AN:

25757

Ashkenazi Jewish (ASJ)

AF:

0.00129

AC:

AN:

17779

East Asian (EAS)

AF:

0.00

AC:

AN:

25377

South Asian (SAS)

AF:

0.0000833

AC:

AN:

48035

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25409

Middle Eastern (MID)

AF:

0.00195

AC:

AN:

3080

European-Non Finnish (NFE)

AF:

0.000231

AC:

187

AN:

810363

Other (OTH)

AF:

0.000394

AC:

AN:

43142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.000300

AC:

AN:

113495

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

AN XY:

35785

show subpopulations

African (AFR)

AF:

0.0000953

AC:

AN:

31470

American (AMR)

AF:

0.000733

AC:

AN:

10919

Ashkenazi Jewish (ASJ)

AF:

0.000752

AC:

AN:

2659

East Asian (EAS)

AF:

0.00

AC:

AN:

3580

South Asian (SAS)

AF:

0.00

AC:

AN:

2897

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6273

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000394

AC:

AN:

53233

Other (OTH)

AF:

0.00

AC:

AN:

1563

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

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:

0.000803

Hom.:

Bravo

AF:

0.000325

ExAC

AF:

0.000249

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

ZFP92-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.73

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.019

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.29

M_CAP

Benign

0.027

MetaRNN

Benign

0.0066

MutationAssessor

Benign

0.0

PhyloP100

-0.55

PrimateAI

Uncertain

0.70

Sift4G

Uncertain

0.027

Polyphen

0.0080

Vest4

0.024

MVP

0.082

MPC

1.0

GERP RS

0.31

Varity_R

0.024

gMVP

0.12

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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