rs725403

Variant names:

• chr8-104697008-A-T
• rs725403
• ENST00000521923.5:n.37-17838A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521923.5(ZFPM2):​n.37-17838A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,998 control chromosomes in the GnomAD database, including 29,956 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29956 hom., cov: 32)
• Consequence: ZFPM2 ENST00000521923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 4 publications found

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

ENSG00000283157 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000521923.5	n.37-17838A>T		intron_variant	Intron 1 of 4	3
ENSG00000283157	ENST00000849119.1	n.82-664T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93838 AN: 151878 Hom.: 29928 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.618 AC: 93909 AN: 151998 Hom.: 29956 Cov.: 32 AF XY: 0.616 AC XY: 45795 AN XY: 74304

African (AFR) AF: 0.479 AC: 19868 AN: 41446

American (AMR) AF: 0.523 AC: 7979 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2221 AN: 3466

East Asian (EAS) AF: 0.505 AC: 2600 AN: 5152

South Asian (SAS) AF: 0.606 AC: 2922 AN: 4820

European-Finnish (FIN) AF: 0.737 AC: 7804 AN: 10582

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48460 AN: 67960

Other (OTH) AF: 0.571 AC: 1208 AN: 2116

Alfa AF: 0.671 Hom.: 4330

Bravo AF: 0.591

Asia WGS AF: 0.561 AC: 1953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.6
DANN	Benign	0.63
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs725403; hg19: chr8-105709236;