ENST00000518180.1:n.196+53069A>G

Variant names:

• chr8-104768044-A-G
• rs9297350
• ENST00000518180.1:n.196+53069A>G

Variant summary

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

The ENST00000518180.1(ZFPM2):​n.196+53069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,176 control chromosomes in the GnomAD database, including 2,323 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 0.16 (2323 hom., cov: 32)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000518180.1	TSL:4	n.196+53069A>G		intron	N/A
	ZFPM2	ENST00000521923.5	TSL:3	n.166+53069A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25056 AN: 152058 Hom.: 2318 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.165 AC: 25065 AN: 152176 Hom.: 2323 Cov.: 32 AF XY: 0.169 AC XY: 12571 AN XY: 74394

African (AFR) AF: 0.105 AC: 4366 AN: 41524

American (AMR) AF: 0.248 AC: 3791 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3472

East Asian (EAS) AF: 0.151 AC: 779 AN: 5170

South Asian (SAS) AF: 0.351 AC: 1689 AN: 4818

European-Finnish (FIN) AF: 0.157 AC: 1663 AN: 10602

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11629 AN: 68002

Other (OTH) AF: 0.187 AC: 394 AN: 2112

Alfa AF: 0.178 Hom.: 1361

Bravo AF: 0.167

Asia WGS AF: 0.225 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.72
PhyloP100		-0.0080

Splicing

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

Other links and lift over

dbSNP: rs9297350; hg19: chr8-105780272;