chr8-105318866-G-GGCGGCGGGAGCGGCGGCGGGA

Variant names:

• chr8-105318866-G-GGCGGCGGGAGCGGCGGCGGGA
• rs71305140
• NM_012082.4:c.-65_-64insGGCGGCGGGAGCGGCGGGAGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_012082.4(ZFPM2):​c.-65_-64insGGCGGCGGGAGCGGCGGGAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: ZFPM2 NM_012082.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37
• 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: G2P, Labcorp Genetics (formerly Invitae)
• 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: Likely_benign. The variant received -1 ACMG points.

• BS2: High AC in GnomAdExome4 at 5 AD,Unknown gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012082.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	NM_012082.4	MANE Select	c.-65_-64insGGCGGCGGGAGCGGCGGGAGC		5_prime_UTR	Exon 1 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.-65_-64insGGCGGCGGGAGCGGCGGGAGC		5_prime_UTR	Exon 1 of 7	NP_001349765.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.-65_-64insGGCGGCGGGAGCGGCGGGAGC		5_prime_UTR	Exon 1 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.-65_-64insGGCGGCGGGAGCGGCGGGAGC		5_prime_UTR	Exon 1 of 8	ENSP00000611435.1
	ZFPM2	ENST00000518180.1	TSL:4	n.479+72348_479+72349insGGCGGCGGGAGCGGCGGGAGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000685 AC: 1 AN: 145902 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000679

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000742 AC: 5 AN: 674268 Hom.: 0 Cov.: 13 AF XY: 0.00000315 AC XY: 1 AN XY: 317362

African (AFR) AF: 0.00 AC: 0 AN: 11216

American (AMR) AF: 0.00 AC: 0 AN: 1036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4266

East Asian (EAS) AF: 0.00 AC: 0 AN: 3578

South Asian (SAS) AF: 0.00 AC: 0 AN: 13836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1320

European-Non Finnish (NFE) AF: 0.00000656 AC: 4 AN: 609922

Other (OTH) AF: 0.0000457 AC: 1 AN: 21862

GnomAD4 genome AF: 0.00000685 AC: 1 AN: 145902 Hom.: 0 Cov.: 0 AF XY: 0.0000141 AC XY: 1 AN XY: 70868

African (AFR) AF: 0.00 AC: 0 AN: 40682

American (AMR) AF: 0.0000679 AC: 1 AN: 14722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 4824

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65704

Other (OTH) AF: 0.00 AC: 0 AN: 2022

Alfa AF: 0.00 Hom.: 1334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

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

Other links and lift over

dbSNP: rs71305140; hg19: chr8-106331094;