rs920628

chr8-105801444-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012082.4(ZFPM2):c.1362A>G(p.Pro454=) 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:4
• Conservation: PhyloP100: -0.167

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

Verdict is Benign. Variant got -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 id is 260171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-105801444-A-G is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFPM2	NM_012082.4	c.1362A>G	p.Pro454=	synonymous_variant	8/8	ENST00000407775.7
ZFPM2-AS1	NR_125797.1	n.191-3002T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFPM2	ENST00000407775.7	c.1362A>G	p.Pro454=	synonymous_variant	8/8	1	NM_012082.4	P1
ZFPM2-AS1	ENST00000520433.5	n.212-3002T>C		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.0462 AC: 11487 AN: 248804 Hom.: 1058 AF XY: 0.0406 AC XY: 5483 AN XY: 134998

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 SAS exome AF: 0.0343

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

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.0459

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.00461

Gnomad4 SAS exome AF: 0.0307

Gnomad4 FIN exome AF: 0.00547

Gnomad4 NFE exome AF: 0.0238

Gnomad4 OTH exome AF: 0.0513

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

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.0784

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.00772

Gnomad4 SAS AF: 0.0322

Gnomad4 FIN AF: 0.00414

Gnomad4 NFE AF: 0.0218

Gnomad4 OTH AF: 0.0962

Alfa AF: 0.0494 Hom.: 859

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 10, 2023	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

46,XY sex reversal 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.14
Dann	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs920628; hg19: chr8-106813672;