rs16873732

Variant names:

• chr8-105801858-T-C
• rs16873732
• NM_012082.4:c.1776T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012082.4(ZFPM2):​c.1776T>C​(p.Pro592Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 1,613,916 control chromosomes in the GnomAD database, including 1,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (460 hom., cov: 32)
  • Exomes 𝑓: 0.027 (901 hom.)
• Consequence: ZFPM2 NM_012082.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.18
• Publications: 7 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-105801858-T-C is Benign according to our data. Variant chr8-105801858-T-C is described in ClinVar as Benign. ClinVar VariationId is 260172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	NM_012082.4	MANE Select	c.1776T>C	p.Pro592Pro	synonymous	Exon 8 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.1617T>C	p.Pro539Pro	synonymous	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.1380T>C	p.Pro460Pro	synonymous	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.1776T>C	p.Pro592Pro	synonymous	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.1773T>C	p.Pro591Pro	synonymous	Exon 8 of 8	ENSP00000611435.1
	ZFPM2	ENST00000517361.1	TSL:2	c.1380T>C	p.Pro460Pro	synonymous	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8429 AN: 152106 Hom.: 455 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0685

Gnomad EAS AF: 0.00792

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0613

GnomAD2 exomes AF: 0.0314 AC: 7820 AN: 249082 AF XY: 0.0294

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0307

Gnomad ASJ exome AF: 0.0717

Gnomad EAS exome AF: 0.00684

Gnomad FIN exome AF: 0.00446

Gnomad NFE exome AF: 0.0220

Gnomad OTH exome AF: 0.0344

GnomAD4 exome AF: 0.0271 AC: 39588 AN: 1461692 Hom.: 901 Cov.: 31 AF XY: 0.0267 AC XY: 19448 AN XY: 727128

African (AFR) AF: 0.142 AC: 4743 AN: 33478

American (AMR) AF: 0.0331 AC: 1481 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 1839 AN: 26136

East Asian (EAS) AF: 0.00458 AC: 182 AN: 39700

South Asian (SAS) AF: 0.0302 AC: 2601 AN: 86258

European-Finnish (FIN) AF: 0.00545 AC: 291 AN: 53402

Middle Eastern (MID) AF: 0.0331 AC: 191 AN: 5768

European-Non Finnish (NFE) AF: 0.0234 AC: 26024 AN: 1111854

Other (OTH) AF: 0.0370 AC: 2236 AN: 60374

GnomAD4 genome AF: 0.0556 AC: 8459 AN: 152224 Hom.: 460 Cov.: 32 AF XY: 0.0540 AC XY: 4021 AN XY: 74428

African (AFR) AF: 0.135 AC: 5609 AN: 41528

American (AMR) AF: 0.0522 AC: 798 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0685 AC: 238 AN: 3472

East Asian (EAS) AF: 0.00775 AC: 40 AN: 5164

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4822

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10624

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0212 AC: 1439 AN: 68006

Other (OTH) AF: 0.0611 AC: 129 AN: 2110

Alfa AF: 0.0351 Hom.: 745

Bravo AF: 0.0633

Asia WGS AF: 0.0550 AC: 190 AN: 3478

EpiCase AF: 0.0254

EpiControl AF: 0.0256

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	46,XY sex reversal 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.66
DANN	Benign	0.62
PhyloP100		-3.2
Mutation Taster		=98/2	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: rs16873732; hg19: chr8-106814086;