rs1554583419

Variant names:

• chr8-105803416-A-G
• rs1554583419
• NM_012082.4:c.3334A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012082.4(ZFPM2):​c.3334A>G​(p.Ser1112Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1112N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047685146).

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.3334A>G	p.Ser1112Gly	missense	Exon 8 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.3175A>G	p.Ser1059Gly	missense	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.2938A>G	p.Ser980Gly	missense	Exon 8 of 8	NP_001349766.1	E7ET52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.3334A>G	p.Ser1112Gly	missense	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.3331A>G	p.Ser1111Gly	missense	Exon 8 of 8	ENSP00000611435.1
	ZFPM2	ENST00000517361.1	TSL:2	c.2938A>G	p.Ser980Gly	missense	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461556 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727052

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111798

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	46,XY sex reversal 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.9
DANN	Benign	0.86
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.013
Sift	Benign	0.25	T
Sift4G	Benign	0.51	T
Polyphen		0.0030	B
Vest4		0.092
MutPred		0.16		Gain of relative solvent accessibility (P = 0.005)
MVP		0.24
MPC		0.092
ClinPred		0.22	T
GERP RS		3.4
Varity_R		0.057
gMVP		0.20
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1554583419; hg19: chr8-106815644;