rs2920048

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.2346G>C(p.Glu782Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,586 control chromosomes in the GnomAD database, including 14,161 homozygotes. 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 0.094 ( 899 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13262 hom. )

Consequence

ZFPM2
NM_012082.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.977

Publications

18 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=0.0012667477).

BP6

Variant 8-105802428-G-C is Benign according to our data. Variant chr8-105802428-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012082.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFPM2	NM_012082.4	MANE Select	c.2346G>C	p.Glu782Asp	missense	Exon 8 of 8	NP_036214.2	Q8WW38-1
ZFPM2	NM_001362836.2		c.2187G>C	p.Glu729Asp	missense	Exon 7 of 7	NP_001349765.1
ZFPM2	NM_001362837.2		c.1950G>C	p.Glu650Asp	missense	Exon 8 of 8	NP_001349766.1	E7ET52

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.2346G>C	p.Glu782Asp	missense	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
ZFPM2	ENST00000941376.1		c.2343G>C	p.Glu781Asp	missense	Exon 8 of 8	ENSP00000611435.1
ZFPM2	ENST00000517361.1	TSL:2	c.1950G>C	p.Glu650Asp	missense	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes

AF:

0.0939

AC:

14282

AN:

152096

Hom.:

898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0886

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0783

Gnomad FIN

AF:

0.0798

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.102

AC:

25169

AN:

247162

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.0685

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.000335

Gnomad FIN exome

AF:

0.0836

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.129

AC:

188747

AN:

1461372

Hom.:

13262

Cov.:

AF XY:

0.129

AC XY:

93506

AN XY:

726934

show subpopulations

African (AFR)

AF:

0.0243

AC:

813

AN:

33476

American (AMR)

AF:

0.0704

AC:

3147

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

3900

AN:

26128

East Asian (EAS)

AF:

0.000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.0850

AC:

7331

AN:

86248

European-Finnish (FIN)

AF:

0.0798

AC:

4251

AN:

53266

Middle Eastern (MID)

AF:

0.149

AC:

859

AN:

5768

European-Non Finnish (NFE)

AF:

0.145

AC:

160942

AN:

1111748

Other (OTH)

AF:

0.124

AC:

7494

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

11783

23567

35350

47134

58917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5616

11232

16848

22464

28080

<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:

0.0938

AC:

14283

AN:

152214

Hom.:

899

Cov.:

AF XY:

0.0889

AC XY:

6619

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0284

AC:

1180

AN:

41556

American (AMR)

AF:

0.0885

AC:

1353

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

498

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.0790

AC:

381

AN:

4824

European-Finnish (FIN)

AF:

0.0798

AC:

845

AN:

10588

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9614

AN:

67998

Other (OTH)

AF:

0.125

AC:

265

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

678

1356

2035

2713

3391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.123

Hom.:

987

Bravo

AF:

0.0929

TwinsUK

AF:

0.146

AC:

541

ALSPAC

AF:

0.145

AC:

560

ESP6500AA

AF:

0.0297

AC:

114

ESP6500EA

AF:

0.137

AC:

1135

ExAC

AF:

0.102

AC:

12290

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

46,XY sex reversal 9 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.8

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.12

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0013

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-0.98

PrimateAI

Benign

0.36

PROVEAN

Benign

0.10

REVEL

Benign

0.19

Sift

Benign

0.68

Sift4G

Benign

0.72

Polyphen

0.0050

Vest4

0.037

MutPred

0.27

Loss of loop (P = 0.1242)

MPC

0.088

ClinPred

0.0012

GERP RS

-7.1

Varity_R

0.035

gMVP

0.093

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over