Genetic Variant ZFPM2:c.-65_-64insGGCGGGAGCGGCGGGAGC (chr8-105318866-G-GGCGGCGGGAGCGGCGGGA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_012082.4(ZFPM2):c.-65_-64insGGCGGGAGCGGCGGGAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000069 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZFPM2
NM_012082.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37

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 Gene-Disease associations (from GenCC):

46,XY sex reversal 9
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
diaphragmatic hernia 3
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
tetralogy of fallot
Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
46,XY partial gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ZFPM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 10 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4 link	c.-65_-64insGGCGGGAGCGGCGGGAGC		5_prime_UTR_variant	Exon 1 of 8	ENST00000407775.7	NP_036214.2	Q8WW38-1Q9NPQ0
ZFPM2	NM_001362836.2 link	c.-65_-64insGGCGGGAGCGGCGGGAGC		5_prime_UTR_variant	Exon 1 of 7		NP_001349765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7 link	c.-65_-64insGGCGGGAGCGGCGGGAGC		5_prime_UTR_variant	Exon 1 of 8	1	NM_012082.4	ENSP00000384179.2		Q8WW38-1
ZFPM2	ENST00000518180.1 link	n.479+72348_479+72349insGGCGGGAGCGGCGGGAGC		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.0000685

AC:

AN:

145902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000172

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:

0.0000304

Gnomad OTH

AF:

0.000495

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000119

AC:

AN:

674268

Hom.:

Cov.:

AF XY:

0.00000945

AC XY:

AN XY:

317362

show subpopulations

African (AFR)

AF:

0.0000892

AC:

AN:

11216

American (AMR)

AF:

0.00

AC:

AN:

1036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4266

East Asian (EAS)

AF:

0.00

AC:

AN:

3578

South Asian (SAS)

AF:

0.00

AC:

AN:

13836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7232

Middle Eastern (MID)

AF:

0.000758

AC:

AN:

1320

European-Non Finnish (NFE)

AF:

0.00000820

AC:

AN:

609922

Other (OTH)

AF:

0.0000457

AC:

AN:

21862

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

GnomAD4 genome

AF:

0.0000685

AC:

AN:

145902

Hom.:

Cov.:

AF XY:

0.0000988

AC XY:

AN XY:

70868

show subpopulations

African (AFR)

AF:

0.000172

AC:

AN:

40682

American (AMR)

AF:

0.00

AC:

AN:

14722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3382

East Asian (EAS)

AF:

0.00

AC:

AN:

4824

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000304

AC:

AN:

65704

Other (OTH)

AF:

0.000495

AC:

AN:

2022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

1334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr8-105318866-G-GGCGGCGGGAGCGGCGGGA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over