Genetic Variant ZFPM2:p.Leu1123Leu (chr8-105803451-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012082.4(ZFPM2):c.3369A>G(p.Leu1123Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,613,764 control chromosomes in the GnomAD database, including 1,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 920 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 846 hom. )

Consequence

ZFPM2
NM_012082.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.256

Variant links:

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 links:

ZFPM2-AS1 (HGNC:50698): (ZFPM2 antisense RNA 1)

ZFPM2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 8-105803451-A-G is Benign according to our data. Variant chr8-105803451-A-G is described in ClinVar as [Benign]. Clinvar id is 414006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.256 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4 link	c.3369A>G	p.Leu1123Leu	synonymous_variant	Exon 8 of 8	ENST00000407775.7	NP_036214.2	Q8WW38-1Q9NPQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7 link	c.3369A>G	p.Leu1123Leu	synonymous_variant	Exon 8 of 8	1	NM_012082.4	ENSP00000384179.2		Q8WW38-1

Frequencies

GnomAD3 genomes

AF:

0.0611

AC:

9294

AN:

152186

Hom.:

917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0276

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000749

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0158

AC:

3919

AN:

248094

Hom.:

374

AF XY:

0.0119

AC XY:

1603

AN XY:

134576

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.000897

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000651

Gnomad OTH exome

AF:

0.00748

GnomAD4 exome

AF:

0.00635

AC:

9276

AN:

1461460

Hom.:

846

Cov.:

AF XY:

0.00546

AC XY:

3967

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.0137

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000440

Gnomad4 OTH exome

AF:

0.0150

GnomAD4 genome

AF:

0.0612

AC:

9327

AN:

152304

Hom.:

920

Cov.:

AF XY:

0.0586

AC XY:

4364

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.211

Gnomad4 AMR

AF:

0.0276

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0353

Hom.:

158

Bravo

AF:

0.0694

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000832

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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

- -

46,XY sex reversal 9

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.3

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over