8-105561411-G-T

Variant names:

• chr8-105561411-G-T
• rs369680006
• NM_012082.4:c.350G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012082.4(ZFPM2):​c.350G>T​(p.Arg117Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R117Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.28
• 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-AS1 (HGNC:50698): (ZFPM2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.350G>T	p.Arg117Leu	missense_variant	Exon 4 of 8	ENST00000407775.7	NP_036214.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.350G>T	p.Arg117Leu	missense_variant	Exon 4 of 8	1	NM_012082.4	ENSP00000384179.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248480 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		8.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.27
Sift	Benign	0.11	T
Sift4G	Uncertain	0.054	T
Polyphen		0.96	D
Vest4		0.87
MutPred		0.56		Loss of ubiquitination at K113 (P = 0.037);
MVP		0.43
MPC		0.46
ClinPred		0.92	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.59
Mutation Taster		=22/78	disease causing

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: rs369680006; hg19: chr8-106573639;