rs6981223

Positions:

• chr8-105502798-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012082.4(ZFPM2):​c.301+58417T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,050 control chromosomes in the GnomAD database, including 12,218 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 0.37 (12218 hom., cov: 32)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.909

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.301+58417T>C		intron_variant		ENST00000407775.7	NP_036214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.301+58417T>C		intron_variant		1	NM_012082.4	ENSP00000384179	P1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55994 AN: 151932 Hom.: 12197 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.369 AC: 56059 AN: 152050 Hom.: 12218 Cov.: 32 AF XY: 0.364 AC XY: 27077 AN XY: 74328

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.364

Alfa AF: 0.310 Hom.: 1686

Bravo AF: 0.381

Asia WGS AF: 0.378 AC: 1313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.9
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6981223; hg19: chr8-106515026;