8-105348445-T-C

Variant names:

• chr8-105348445-T-C
• rs2957452
• NM_012082.4:c.40+29464T>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.40+29464T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,192 control chromosomes in the GnomAD database, including 52,470 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 0.83 (52470 hom., cov: 32)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.40+29464T>C		intron_variant	Intron 1 of 7	ENST00000407775.7	NP_036214.2
ZFPM2	NM_001362836.2	c.40+29464T>C		intron_variant	Intron 1 of 6		NP_001349765.1
ZFPM2	NM_001362837.2	c.-357+28691T>C		intron_variant	Intron 1 of 7		NP_001349766.1
ZFPM2	XM_047421634.1	c.-357+28909T>C		intron_variant	Intron 1 of 7		XP_047277590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.40+29464T>C		intron_variant	Intron 1 of 7	1	NM_012082.4	ENSP00000384179.2
ZFPM2	ENST00000520492.5	c.-357+28691T>C		intron_variant	Intron 1 of 7	2		ENSP00000430757.1
ZFPM2	ENST00000518180.1	n.480-70699T>C		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126066 AN: 152074 Hom.: 52423 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.829 AC: 126172 AN: 152192 Hom.: 52470 Cov.: 32 AF XY: 0.834 AC XY: 62066 AN XY: 74406

African (AFR) AF: 0.792 AC: 32857 AN: 41512

American (AMR) AF: 0.866 AC: 13240 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2920 AN: 3470

East Asian (EAS) AF: 0.969 AC: 5013 AN: 5174

South Asian (SAS) AF: 0.882 AC: 4256 AN: 4826

European-Finnish (FIN) AF: 0.888 AC: 9417 AN: 10608

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55609 AN: 67992

Other (OTH) AF: 0.850 AC: 1797 AN: 2114

Alfa AF: 0.826 Hom.: 28330

Bravo AF: 0.827

Asia WGS AF: 0.922 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		0.0
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: rs2957452; hg19: chr8-106360673;