8-105801288-T-A

Variant names:

• chr8-105801288-T-A
• rs606231252
• NM_012082.4:c.1206T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_012082.4(ZFPM2):​c.1206T>A​(p.Ser402Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.0410
• Publications: 6 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-105801288-T-A is Pathogenic according to our data. Variant chr8-105801288-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 156583.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.060569525). . Strength limited to SUPPORTING due to the PP5.

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.1206T>A	p.Ser402Arg	missense	Exon 8 of 8	NP_036214.2
	ZFPM2	NM_001362836.2		c.1047T>A	p.Ser349Arg	missense	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.810T>A	p.Ser270Arg	missense	Exon 8 of 8	NP_001349766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.1206T>A	p.Ser402Arg	missense	Exon 8 of 8	ENSP00000384179.2
	ZFPM2	ENST00000517361.1	TSL:2	c.810T>A	p.Ser270Arg	missense	Exon 6 of 6	ENSP00000428720.1
	ZFPM2	ENST00000520492.5	TSL:2	c.810T>A	p.Ser270Arg	missense	Exon 8 of 8	ENSP00000430757.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

46,XY sex reversal 9 Pathogenic:1

Jul 15, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.71
DANN	Benign	0.82
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.29	N
PhyloP100		-0.041
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Pathogenic	0.66
Sift	Benign	0.57	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.34
MutPred		0.21		Loss of phosphorylation at S402 (P = 0.0123)
MVP		0.22
MPC		0.11
ClinPred		0.049	T
GERP RS		-2.1
Varity_R		0.083
gMVP		0.25
Mutation Taster		=10/90	disease causing (ClinVar)

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: rs606231252; hg19: chr8-106813516;