NM_012082.4:c.2976T>C

Variant names:

• chr8-105803058-T-C
• rs1442320
• NM_012082.4:c.2976T>C

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.2976T>C​(p.Tyr992Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 1,613,690 control chromosomes in the GnomAD database, including 1,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (456 hom., cov: 32)
  • Exomes 𝑓: 0.027 (902 hom.)
• Consequence: ZFPM2 NM_012082.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.493
• Publications: 8 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=-0.79).
• BP6: Variant 8-105803058-T-C is Benign according to our data. Variant chr8-105803058-T-C is described in ClinVar as Benign. ClinVar VariationId is 260176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.493 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 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.2976T>C	p.Tyr992Tyr	synonymous	Exon 8 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.2817T>C	p.Tyr939Tyr	synonymous	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.2580T>C	p.Tyr860Tyr	synonymous	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.2976T>C	p.Tyr992Tyr	synonymous	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.2973T>C	p.Tyr991Tyr	synonymous	Exon 8 of 8	ENSP00000611435.1
	ZFPM2	ENST00000517361.1	TSL:2	c.2580T>C	p.Tyr860Tyr	synonymous	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8417 AN: 152126 Hom.: 451 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0608

GnomAD2 exomes AF: 0.0313 AC: 7787 AN: 248408 AF XY: 0.0294

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0307

Gnomad ASJ exome AF: 0.0717

Gnomad EAS exome AF: 0.00688

Gnomad FIN exome AF: 0.00446

Gnomad NFE exome AF: 0.0220

Gnomad OTH exome AF: 0.0345

GnomAD4 exome AF: 0.0271 AC: 39595 AN: 1461446 Hom.: 902 Cov.: 32 AF XY: 0.0267 AC XY: 19442 AN XY: 726980

African (AFR) AF: 0.142 AC: 4751 AN: 33472

American (AMR) AF: 0.0331 AC: 1480 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 1835 AN: 26108

East Asian (EAS) AF: 0.00459 AC: 182 AN: 39668

South Asian (SAS) AF: 0.0302 AC: 2601 AN: 86232

European-Finnish (FIN) AF: 0.00545 AC: 291 AN: 53390

Middle Eastern (MID) AF: 0.0331 AC: 191 AN: 5766

European-Non Finnish (NFE) AF: 0.0234 AC: 26028 AN: 1111768

Other (OTH) AF: 0.0370 AC: 2236 AN: 60366

GnomAD4 genome AF: 0.0555 AC: 8447 AN: 152244 Hom.: 456 Cov.: 32 AF XY: 0.0540 AC XY: 4021 AN XY: 74470

African (AFR) AF: 0.135 AC: 5601 AN: 41522

American (AMR) AF: 0.0523 AC: 799 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3468

East Asian (EAS) AF: 0.00773 AC: 40 AN: 5176

South Asian (SAS) AF: 0.0302 AC: 146 AN: 4832

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10622

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0211 AC: 1436 AN: 68018

Other (OTH) AF: 0.0607 AC: 128 AN: 2110

Alfa AF: 0.0347 Hom.: 425

Bravo AF: 0.0633

Asia WGS AF: 0.0550 AC: 190 AN: 3478

EpiCase AF: 0.0256

EpiControl AF: 0.0256

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	46,XY sex reversal 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.68
DANN	Benign	0.55
PhyloP100		-0.49
Mutation Taster		=91/9	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: rs1442320; hg19: chr8-106815286;