rs146423225

Variant names:

• chr8-105802747-C-G
• rs146423225
• NM_012082.4:c.2665C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-105802747-C-G
• chr8-105802747-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012082.4(ZFPM2):​c.2665C>G​(p.Gln889Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,613,490 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (18 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (112 hom.)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.25
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001937449).
• BP6: Variant 8-105802747-C-G is Benign according to our data. Variant chr8-105802747-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 240843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.05 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.2665C>G	p.Gln889Glu	missense	Exon 8 of 8	NP_036214.2
	ZFPM2	NM_001362836.2		c.2506C>G	p.Gln836Glu	missense	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.2269C>G	p.Gln757Glu	missense	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.2665C>G	p.Gln889Glu	missense	Exon 8 of 8	ENSP00000384179.2
	ZFPM2	ENST00000517361.1	TSL:2	c.2269C>G	p.Gln757Glu	missense	Exon 6 of 6	ENSP00000428720.1
	ZFPM2	ENST00000520492.5	TSL:2	c.2269C>G	p.Gln757Glu	missense	Exon 8 of 8	ENSP00000430757.1

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 795 AN: 152154 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.0105 AC: 2605 AN: 247732 AF XY: 0.00812

Gnomad AFR exome AF: 0.000654

Gnomad AMR exome AF: 0.0565

Gnomad ASJ exome AF: 0.000897

Gnomad EAS exome AF: 0.000335

Gnomad FIN exome AF: 0.0234

Gnomad NFE exome AF: 0.000704

Gnomad OTH exome AF: 0.00666

GnomAD4 exome AF: 0.00285 AC: 4158 AN: 1461218 Hom.: 112 Cov.: 32 AF XY: 0.00255 AC XY: 1852 AN XY: 726854

African (AFR) AF: 0.000538 AC: 18 AN: 33478

American (AMR) AF: 0.0518 AC: 2310 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26120

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39654

South Asian (SAS) AF: 0.000859 AC: 74 AN: 86168

European-Finnish (FIN) AF: 0.0231 AC: 1229 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000291 AC: 323 AN: 1111744

Other (OTH) AF: 0.00267 AC: 161 AN: 60364

GnomAD4 genome AF: 0.00524 AC: 798 AN: 152272 Hom.: 18 Cov.: 32 AF XY: 0.00637 AC XY: 474 AN XY: 74448

African (AFR) AF: 0.000842 AC: 35 AN: 41568

American (AMR) AF: 0.0267 AC: 409 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5152

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.0231 AC: 245 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00119 AC: 81 AN: 68030

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00100 Hom.: 2

Bravo AF: 0.00650

ESP6500AA AF: 0.000514 AC: 2

ESP6500EA AF: 0.000724 AC: 6

ExAC AF: 0.00812 AC: 982

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jun 17, 2024

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 29, 2018

Genetic Services Laboratory, University of Chicago

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
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.046
Sift	Benign	0.035	D
Sift4G	Uncertain	0.046	D
Polyphen		0.0020	B
Vest4		0.22
MPC		0.11
ClinPred		0.017	T
GERP RS		5.6
Varity_R		0.087
gMVP		0.27
Mutation Taster		=99/1	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: rs146423225; hg19: chr8-106814975;