NM_012082.4:c.1969A>G

Variant names:

• chr8-105802051-A-G
• rs28374544
• NM_012082.4:c.1969A>G

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.1969A>G​(p.Ser657Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00783 in 1,613,788 control chromosomes in the GnomAD database, including 824 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (425 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (399 hom.)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:5
• Conservation: PhyloP100: 4.99
• Publications: 16 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=0.002689898).
• BP6: Variant 8-105802051-A-G is Benign according to our data. Variant chr8-105802051-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 6127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	NM_012082.4	MANE Select	c.1969A>G	p.Ser657Gly	missense	Exon 8 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.1810A>G	p.Ser604Gly	missense	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.1573A>G	p.Ser525Gly	missense	Exon 8 of 8	NP_001349766.1	E7ET52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.1969A>G	p.Ser657Gly	missense	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.1966A>G	p.Ser656Gly	missense	Exon 8 of 8	ENSP00000611435.1
	ZFPM2	ENST00000517361.1	TSL:2	c.1573A>G	p.Ser525Gly	missense	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6281 AN: 152134 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0282

GnomAD2 exomes AF: 0.0106 AC: 2620 AN: 247912 AF XY: 0.00800

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.00857

Gnomad ASJ exome AF: 0.000897

Gnomad EAS exome AF: 0.0000559

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000464

Gnomad OTH exome AF: 0.00481

GnomAD4 exome AF: 0.00434 AC: 6350 AN: 1461536 Hom.: 399 Cov.: 31 AF XY: 0.00376 AC XY: 2732 AN XY: 727036

African (AFR) AF: 0.144 AC: 4823 AN: 33478

American (AMR) AF: 0.00955 AC: 427 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.000995 AC: 26 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39676

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00659 AC: 38 AN: 5768

European-Non Finnish (NFE) AF: 0.000353 AC: 392 AN: 1111840

Other (OTH) AF: 0.0101 AC: 611 AN: 60372

GnomAD4 genome AF: 0.0413 AC: 6290 AN: 152252 Hom.: 425 Cov.: 32 AF XY: 0.0386 AC XY: 2872 AN XY: 74438

African (AFR) AF: 0.141 AC: 5863 AN: 41528

American (AMR) AF: 0.0203 AC: 311 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68028

Other (OTH) AF: 0.0279 AC: 59 AN: 2112

Alfa AF: 0.0120 Hom.: 252

Bravo AF: 0.0470

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.131 AC: 486

ESP6500EA AF: 0.000731 AC: 6

ExAC AF: 0.0125 AC: 1515

Asia WGS AF: 0.00808 AC: 29 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000712

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	46,XY sex reversal 9 (2)
-	-	1	not provided (1)
-	-	1	not specified (1)
1	-	-	Tetralogy of Fallot (1)
-	-	1	Tetralogy of Fallot;C1857781:Diaphragmatic hernia 3;C4015129:46,XY sex reversal 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.0
DANN	Benign	0.86
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.58
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		5.0
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.094
Sift	Benign	0.36	T
Sift4G	Benign	0.21	T
Polyphen		0.020	B
Vest4		0.041
MPC		0.096
ClinPred		0.020	T
GERP RS		4.4
Varity_R		0.041
gMVP		0.18
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: rs28374544; hg19: chr8-106814279; COSMIC: COSV65874397;