NM_012082.4:c.2346G>C

Variant names:

• chr8-105802428-G-C
• rs2920048
• NM_012082.4:c.2346G>C

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.2346G>C​(p.Glu782Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,586 control chromosomes in the GnomAD database, including 14,161 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 0.094 (899 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13262 hom.)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.977
• Publications: 18 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=0.0012667477).
• BP6: Variant 8-105802428-G-C is Benign according to our data. Variant chr8-105802428-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 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.2346G>C	p.Glu782Asp	missense	Exon 8 of 8	NP_036214.2
	ZFPM2	NM_001362836.2		c.2187G>C	p.Glu729Asp	missense	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.1950G>C	p.Glu650Asp	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.2346G>C	p.Glu782Asp	missense	Exon 8 of 8	ENSP00000384179.2
	ZFPM2	ENST00000517361.1	TSL:2	c.1950G>C	p.Glu650Asp	missense	Exon 6 of 6	ENSP00000428720.1
	ZFPM2	ENST00000520492.5	TSL:2	c.1950G>C	p.Glu650Asp	missense	Exon 8 of 8	ENSP00000430757.1

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 14282 AN: 152096 Hom.: 898 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0798

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.128

GnomAD2 exomes AF: 0.102 AC: 25169 AN: 247162 AF XY: 0.105

Gnomad AFR exome AF: 0.0257

Gnomad AMR exome AF: 0.0685

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.000335

Gnomad FIN exome AF: 0.0836

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.129 AC: 188747 AN: 1461372 Hom.: 13262 Cov.: 33 AF XY: 0.129 AC XY: 93506 AN XY: 726934

African (AFR) AF: 0.0243 AC: 813 AN: 33476

American (AMR) AF: 0.0704 AC: 3147 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3900 AN: 26128

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39684

South Asian (SAS) AF: 0.0850 AC: 7331 AN: 86248

European-Finnish (FIN) AF: 0.0798 AC: 4251 AN: 53266

Middle Eastern (MID) AF: 0.149 AC: 859 AN: 5768

European-Non Finnish (NFE) AF: 0.145 AC: 160942 AN: 1111748

Other (OTH) AF: 0.124 AC: 7494 AN: 60366

GnomAD4 genome AF: 0.0938 AC: 14283 AN: 152214 Hom.: 899 Cov.: 32 AF XY: 0.0889 AC XY: 6619 AN XY: 74418

African (AFR) AF: 0.0284 AC: 1180 AN: 41556

American (AMR) AF: 0.0885 AC: 1353 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 498 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0790 AC: 381 AN: 4824

European-Finnish (FIN) AF: 0.0798 AC: 845 AN: 10588

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9614 AN: 67998

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.123 Hom.: 987

Bravo AF: 0.0929

TwinsUK AF: 0.146 AC: 541

ALSPAC AF: 0.145 AC: 560

ESP6500AA AF: 0.0297 AC: 114

ESP6500EA AF: 0.137 AC: 1135

ExAC AF: 0.102 AC: 12290

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Oct 23, 2023

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Apr 17, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

46,XY sex reversal 9 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.72
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.98
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.19
Sift	Benign	0.68	T
Sift4G	Benign	0.72	T
Polyphen		0.0050	B
Vest4		0.037
MutPred		0.27		Loss of loop (P = 0.1242)
MPC		0.088
ClinPred		0.0012	T
GERP RS		-7.1
Varity_R		0.035
gMVP		0.093
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: rs2920048; hg19: chr8-106814656; COSMIC: COSV65873723;