chr8-105130105-C-T

Variant names:

• chr8-105130105-C-T
• rs9297357
• ENST00000518180.1:n.243-116188C>T

Variant summary

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

The ENST00000518180.1(ZFPM2):​n.243-116188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,134 control chromosomes in the GnomAD database, including 41,130 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 0.73 (41130 hom., cov: 33)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 9 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518180.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000518180.1	TSL:4	n.243-116188C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111691 AN: 152016 Hom.: 41104 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.735 AC: 111774 AN: 152134 Hom.: 41130 Cov.: 33 AF XY: 0.735 AC XY: 54690 AN XY: 74380

African (AFR) AF: 0.753 AC: 31230 AN: 41478

American (AMR) AF: 0.679 AC: 10362 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2736 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3984 AN: 5170

South Asian (SAS) AF: 0.725 AC: 3495 AN: 4820

European-Finnish (FIN) AF: 0.771 AC: 8182 AN: 10608

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49255 AN: 67998

Other (OTH) AF: 0.746 AC: 1578 AN: 2114

Alfa AF: 0.726 Hom.: 122766

Bravo AF: 0.726

Asia WGS AF: 0.772 AC: 2683 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.21
PhyloP100		-0.24

Splicing

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

Other links and lift over

dbSNP: rs9297357; hg19: chr8-106142333;