Genetic Variant ZFPM2:p.Gln145Arg (chr8-105634259-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012082.4(ZFPM2):c.434A>G(p.Gln145Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q145P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZFPM2
NM_012082.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.21

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.119692475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4 link	c.434A>G	p.Gln145Arg	missense_variant	Exon 5 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.434A>G	p.Gln145Arg	missense_variant	Exon 5 of 8	1	NM_012082.4	ENSP00000384179.2		Q8WW38-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246584

AF XY:

0.00000748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

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:

0.00000137

AC:

AN:

1459742

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725892

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.0000449

AC:

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

85714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111024

Other (OTH)

AF:

0.00

AC:

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.16

T;T;.;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.65

T;.;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.;.

PhyloP100

2.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.53

N;N;D;N

REVEL

Benign

0.039

Sift

Benign

0.52

T;T;.;T

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.016

B;.;.;.

Vest4

0.24

MutPred

0.33

Gain of MoRF binding (P = 0.0157);.;.;.;

MVP

0.51

MPC

0.10

ClinPred

0.056

GERP RS

1.4

Varity_R

0.12

gMVP

0.21

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over