rs1442320

Positions:

• chr8-105803058-T-C

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.2976T>C​(p.Tyr992=) 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 1,613,690 control chromosomes in the GnomAD database, including 1,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (456 hom., cov: 32)
  • Exomes 𝑓: 0.027 (902 hom.)
• Consequence: ZFPM2 NM_012082.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.493

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=-0.79).
• BP6: Variant 8-105803058-T-C is Benign according to our data. Variant chr8-105803058-T-C is described in ClinVar as [Benign]. Clinvar id is 260176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-105803058-T-C is described in Lovd as [Likely_benign]. Variant chr8-105803058-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.493 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.2976T>C	p.Tyr992=	synonymous_variant	8/8	ENST00000407775.7	NP_036214.2
ZFPM2-AS1	NR_125797.1	n.191-4616A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.2976T>C	p.Tyr992=	synonymous_variant	8/8	1	NM_012082.4	ENSP00000384179	P1
ZFPM2-AS1	ENST00000520433.5	n.212-4616A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8417 AN: 152126 Hom.: 451 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0608

GnomAD3 exomes AF: 0.0313 AC: 7787 AN: 248408 Hom.: 294 AF XY: 0.0294 AC XY: 3959 AN XY: 134780

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0307

Gnomad ASJ exome AF: 0.0717

Gnomad EAS exome AF: 0.00688

Gnomad SAS exome AF: 0.0337

Gnomad FIN exome AF: 0.00446

Gnomad NFE exome AF: 0.0220

Gnomad OTH exome AF: 0.0345

GnomAD4 exome AF: 0.0271 AC: 39595 AN: 1461446 Hom.: 902 Cov.: 32 AF XY: 0.0267 AC XY: 19442 AN XY: 726980

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0331

Gnomad4 ASJ exome AF: 0.0703

Gnomad4 EAS exome AF: 0.00459

Gnomad4 SAS exome AF: 0.0302

Gnomad4 FIN exome AF: 0.00545

Gnomad4 NFE exome AF: 0.0234

Gnomad4 OTH exome AF: 0.0370

GnomAD4 genome AF: 0.0555 AC: 8447 AN: 152244 Hom.: 456 Cov.: 32 AF XY: 0.0540 AC XY: 4021 AN XY: 74470

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0523

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.00773

Gnomad4 SAS AF: 0.0302

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.0607

Alfa AF: 0.0349 Hom.: 168

Bravo AF: 0.0633

Asia WGS AF: 0.0550 AC: 190 AN: 3478

EpiCase AF: 0.0256

EpiControl AF: 0.0256

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Jul 03, 2023	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

46,XY sex reversal 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.68
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: rs1442320; hg19: chr8-106815286;