rs920628

Variant names:

• chr8-105801444-A-G
• rs920628
• NM_012082.4:c.1362A>G

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.1362A>G​(p.Pro454Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 1,613,784 control chromosomes in the GnomAD database, including 5,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2406 hom., cov: 32)
  • Exomes 𝑓: 0.033 (2704 hom.)
• Consequence: ZFPM2 NM_012082.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.167
• Publications: 5 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=-0.7).
• BP6: Variant 8-105801444-A-G is Benign according to our data. Variant chr8-105801444-A-G is described in ClinVar as Benign. ClinVar VariationId is 260171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.167 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	NM_012082.4	MANE Select	c.1362A>G	p.Pro454Pro	synonymous	Exon 8 of 8	NP_036214.2
	ZFPM2	NM_001362836.2		c.1203A>G	p.Pro401Pro	synonymous	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.966A>G	p.Pro322Pro	synonymous	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.1362A>G	p.Pro454Pro	synonymous	Exon 8 of 8	ENSP00000384179.2
	ZFPM2	ENST00000517361.1	TSL:2	c.966A>G	p.Pro322Pro	synonymous	Exon 6 of 6	ENSP00000428720.1
	ZFPM2	ENST00000520492.5	TSL:2	c.966A>G	p.Pro322Pro	synonymous	Exon 8 of 8	ENSP00000430757.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17092 AN: 152026 Hom.: 2387 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0967

GnomAD2 exomes AF: 0.0462 AC: 11487 AN: 248804 AF XY: 0.0406

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.0423

Gnomad ASJ exome AF: 0.0727

Gnomad EAS exome AF: 0.00693

Gnomad FIN exome AF: 0.00446

Gnomad NFE exome AF: 0.0226

Gnomad OTH exome AF: 0.0417

GnomAD4 exome AF: 0.0331 AC: 48333 AN: 1461640 Hom.: 2704 Cov.: 31 AF XY: 0.0319 AC XY: 23197 AN XY: 727102

African (AFR) AF: 0.342 AC: 11444 AN: 33478

American (AMR) AF: 0.0459 AC: 2050 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 1865 AN: 26134

East Asian (EAS) AF: 0.00461 AC: 183 AN: 39692

South Asian (SAS) AF: 0.0307 AC: 2644 AN: 86252

European-Finnish (FIN) AF: 0.00547 AC: 292 AN: 53398

Middle Eastern (MID) AF: 0.0439 AC: 253 AN: 5768

European-Non Finnish (NFE) AF: 0.0238 AC: 26504 AN: 1111838

Other (OTH) AF: 0.0513 AC: 3098 AN: 60372

GnomAD4 genome AF: 0.113 AC: 17156 AN: 152144 Hom.: 2406 Cov.: 32 AF XY: 0.109 AC XY: 8093 AN XY: 74398

African (AFR) AF: 0.332 AC: 13766 AN: 41432

American (AMR) AF: 0.0784 AC: 1199 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3472

East Asian (EAS) AF: 0.00772 AC: 40 AN: 5178

South Asian (SAS) AF: 0.0322 AC: 155 AN: 4820

European-Finnish (FIN) AF: 0.00414 AC: 44 AN: 10620

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0218 AC: 1486 AN: 68020

Other (OTH) AF: 0.0962 AC: 203 AN: 2110

Alfa AF: 0.0579 Hom.: 2688

Bravo AF: 0.128

Asia WGS AF: 0.0670 AC: 234 AN: 3478

EpiCase AF: 0.0261

EpiControl AF: 0.0264

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 10, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 17, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

46,XY sex reversal 9 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.14
DANN	Benign	0.55
PhyloP100		-0.17
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: rs920628; hg19: chr8-106813672;