rs6981223

Variant names:

• chr8-105502798-T-C
• rs6981223
• NM_012082.4:c.301+58417T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.301+58417T>C		intron_variant	Intron 3 of 7	ENST00000407775.7	NP_036214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.301+58417T>C		intron_variant	Intron 3 of 7	1	NM_012082.4	ENSP00000384179.2

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

African (AFR) AF: 0.617 AC: 25583 AN: 41460

American (AMR) AF: 0.310 AC: 4740 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3466

East Asian (EAS) AF: 0.306 AC: 1574 AN: 5148

South Asian (SAS) AF: 0.358 AC: 1724 AN: 4820

European-Finnish (FIN) AF: 0.234 AC: 2471 AN: 10578

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17631 AN: 67976

Other (OTH) AF: 0.364 AC: 767 AN: 2110

Alfa AF: 0.311 Hom.: 2897

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
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6981223; hg19: chr8-106515026;