8-105803451-A-G

Variant names:

• chr8-105803451-A-G
• rs16873744
• NM_012082.4:c.3369A>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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.256
• Publications: 4 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=-0.67).
• BP6: Variant 8-105803451-A-G is Benign according to our data. Variant chr8-105803451-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

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.3369A>G	p.Leu1123Leu	synonymous	Exon 8 of 8	NP_036214.2
	ZFPM2	NM_001362836.2		c.3210A>G	p.Leu1070Leu	synonymous	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.2973A>G	p.Leu991Leu	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.3369A>G	p.Leu1123Leu	synonymous	Exon 8 of 8	ENSP00000384179.2
	ZFPM2	ENST00000517361.1	TSL:2	c.2973A>G	p.Leu991Leu	synonymous	Exon 6 of 6	ENSP00000428720.1
	ZFPM2	ENST00000520492.5	TSL:2	c.2973A>G	p.Leu991Leu	synonymous	Exon 8 of 8	ENSP00000430757.1

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9294 AN: 152186 Hom.: 917 Cov.: 32

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

GnomAD2 exomes AF: 0.0158 AC: 3919 AN: 248094 AF XY: 0.0119

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 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.: 32 AF XY: 0.00546 AC XY: 3967 AN XY: 726976

African (AFR) AF: 0.213 AC: 7129 AN: 33468

American (AMR) AF: 0.0137 AC: 611 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.000957 AC: 25 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39672

South Asian (SAS) AF: 0.000568 AC: 49 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5768

European-Non Finnish (NFE) AF: 0.000440 AC: 489 AN: 1111766

Other (OTH) AF: 0.0150 AC: 908 AN: 60364

GnomAD4 genome AF: 0.0612 AC: 9327 AN: 152304 Hom.: 920 Cov.: 32 AF XY: 0.0586 AC XY: 4364 AN XY: 74488

African (AFR) AF: 0.211 AC: 8750 AN: 41542

American (AMR) AF: 0.0276 AC: 422 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68038

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0525 Hom.: 565

Bravo AF: 0.0694

Asia WGS AF: 0.0120 AC: 44 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000832

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.3
DANN	Benign	0.73
PhyloP100		-0.26
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: rs16873744; hg19: chr8-106815679;