rs11993776

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012082.4(ZFPM2):c.1208C>G(p.Ala403Gly) variant causes a missense change. The variant allele was found at a frequency of 0.109 in 1,613,686 control chromosomes in the GnomAD database, including 13,171 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3722 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9449 hom. )

Consequence

ZFPM2
NM_012082.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.12

Publications

22 publications found

Variant links:

Genes affected

ZFPM2 (HGNC:16700): (zinc finger protein, FOG family member 2) The zinc finger protein encoded by this gene is a widely expressed member of the FOG family of transcription factors. The family members modulate the activity of GATA family proteins, which are important regulators of hematopoiesis and cardiogenesis in mammals. It has been demonstrated that the protein can both activate and down-regulate expression of GATA-target genes, suggesting different modulation in different promoter contexts. A related mRNA suggests an alternatively spliced product but this information is not yet fully supported by the sequence. [provided by RefSeq, Jul 2008]

ZFPM2 links:

ZFPM2-AS1 (HGNC:50698): (ZFPM2 antisense RNA 1)

ZFPM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036206841).

BP6

Variant 8-105801290-C-G is Benign according to our data. Variant chr8-105801290-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4 link	c.1208C>G	p.Ala403Gly	missense_variant	Exon 8 of 8	ENST00000407775.7	NP_036214.2	Q8WW38-1Q9NPQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7 link	c.1208C>G	p.Ala403Gly	missense_variant	Exon 8 of 8	1	NM_012082.4	ENSP00000384179.2		Q8WW38-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26745

AN:

151892

Hom.:

3699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.0685

Gnomad FIN

AF:

0.0686

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0913

Gnomad OTH

AF:

0.160

GnomAD2 exomes

AF:

0.110

AC:

27377

AN:

249044

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.0780

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.0799

Gnomad NFE exome

AF:

0.0910

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.102

AC:

148490

AN:

1461676

Hom.:

9449

Cov.:

AF XY:

0.0996

AC XY:

72417

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.393

AC:

13173

AN:

33480

American (AMR)

AF:

0.0824

AC:

3686

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

2941

AN:

26136

East Asian (EAS)

AF:

0.163

AC:

6482

AN:

39696

South Asian (SAS)

AF:

0.0778

AC:

6707

AN:

86258

European-Finnish (FIN)

AF:

0.0806

AC:

4303

AN:

53398

Middle Eastern (MID)

AF:

0.0843

AC:

486

AN:

5768

European-Non Finnish (NFE)

AF:

0.0931

AC:

103543

AN:

1111848

Other (OTH)

AF:

0.119

AC:

7169

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

9271

18542

27814

37085

46356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4036

8072

12108

16144

20180

<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:

0.176

AC:

26827

AN:

152010

Hom.:

3722

Cov.:

AF XY:

0.172

AC XY:

12758

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.388

AC:

16053

AN:

41390

American (AMR)

AF:

0.132

AC:

2010

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

398

AN:

3470

East Asian (EAS)

AF:

0.138

AC:

710

AN:

5158

South Asian (SAS)

AF:

0.0682

AC:

328

AN:

4812

European-Finnish (FIN)

AF:

0.0686

AC:

727

AN:

10600

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0913

AC:

6209

AN:

67990

Other (OTH)

AF:

0.164

AC:

347

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

941

1882

2823

3764

4705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.106

Hom.:

845

Bravo

AF:

0.190

TwinsUK

AF:

0.0984

AC:

365

ALSPAC

AF:

0.0939

AC:

362

ESP6500AA

AF:

0.357

AC:

1423

ESP6500EA

AF:

0.0941

AC:

787

ExAC

AF:

0.115

AC:

13842

Asia WGS

AF:

0.145

AC:

505

AN:

3478

EpiCase

AF:

0.0911

EpiControl

AF:

0.0904

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

46,XY sex reversal 9

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.13

T;T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.26

T;.;T

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.9

N;.;.

PhyloP100

4.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.030

N;N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.87

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.019

MPC

0.097

ClinPred

0.0021

GERP RS

4.0

Varity_R

0.040

gMVP

0.25

Mutation Taster

=99/1

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over