8-105544406-A-G

Variant names:

• chr8-105544406-A-G
• rs1349319
• NM_012082.4:c.302-16957A>G

Variant summary

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

The NM_012082.4(ZFPM2):​c.302-16957A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,024 control chromosomes in the GnomAD database, including 38,310 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 0.70 (38310 hom., cov: 31)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 3 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

LOC105375696 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	NM_012082.4	MANE Select	c.302-16957A>G		intron	N/A	NP_036214.2
	ZFPM2	NM_001362836.2		c.143-16957A>G		intron	N/A	NP_001349765.1
	ZFPM2	NM_001362837.2		c.-95-16957A>G		intron	N/A	NP_001349766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.302-16957A>G		intron	N/A	ENSP00000384179.2
	ZFPM2	ENST00000511341.6	TSL:1	n.1042-16957A>G		intron	N/A
	ZFPM2	ENST00000517361.1	TSL:2	c.-96+15437A>G		intron	N/A	ENSP00000428720.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105728 AN: 151904 Hom.: 38261 Cov.: 31

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.696 AC: 105837 AN: 152024 Hom.: 38310 Cov.: 31 AF XY: 0.693 AC XY: 51497 AN XY: 74290

African (AFR) AF: 0.921 AC: 38233 AN: 41530

American (AMR) AF: 0.618 AC: 9425 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2178 AN: 3468

East Asian (EAS) AF: 0.650 AC: 3349 AN: 5150

South Asian (SAS) AF: 0.751 AC: 3618 AN: 4816

European-Finnish (FIN) AF: 0.592 AC: 6256 AN: 10562

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.598 AC: 40641 AN: 67930

Other (OTH) AF: 0.668 AC: 1414 AN: 2116

Alfa AF: 0.664 Hom.: 5991

Bravo AF: 0.700

Asia WGS AF: 0.758 AC: 2627 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.4
DANN	Benign	0.66
PhyloP100		0.22
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: rs1349319; hg19: chr8-106556634;