8-105802467-C-G

Variant names:

• chr8-105802467-C-G
• rs35998713
• NM_012082.4:c.2385C>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.2385C>G​(p.Val795Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,613,404 control chromosomes in the GnomAD database, including 1,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (455 hom., cov: 32)
  • Exomes 𝑓: 0.027 (893 hom.)
• Consequence: ZFPM2 NM_012082.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.13
• Publications: 6 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=-0.56).
• BP6: Variant 8-105802467-C-G is Benign according to our data. Variant chr8-105802467-C-G is described in ClinVar as Benign. ClinVar VariationId is 260175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.13 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.2385C>G	p.Val795Val	synonymous	Exon 8 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.2226C>G	p.Val742Val	synonymous	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.1989C>G	p.Val663Val	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.2385C>G	p.Val795Val	synonymous	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.2382C>G	p.Val794Val	synonymous	Exon 8 of 8	ENSP00000611435.1
	ZFPM2	ENST00000517361.1	TSL:2	c.1989C>G	p.Val663Val	synonymous	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8409 AN: 152140 Hom.: 450 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0685

Gnomad EAS AF: 0.00791

Gnomad SAS AF: 0.0282

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0612

GnomAD2 exomes AF: 0.0311 AC: 7681 AN: 247142 AF XY: 0.0291

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0307

Gnomad ASJ exome AF: 0.0714

Gnomad EAS exome AF: 0.00688

Gnomad FIN exome AF: 0.00446

Gnomad NFE exome AF: 0.0219

Gnomad OTH exome AF: 0.0344

GnomAD4 exome AF: 0.0269 AC: 39312 AN: 1461146 Hom.: 893 Cov.: 32 AF XY: 0.0265 AC XY: 19275 AN XY: 726768

African (AFR) AF: 0.142 AC: 4737 AN: 33468

American (AMR) AF: 0.0330 AC: 1474 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 1834 AN: 26106

East Asian (EAS) AF: 0.00456 AC: 181 AN: 39664

South Asian (SAS) AF: 0.0288 AC: 2478 AN: 86182

European-Finnish (FIN) AF: 0.00546 AC: 291 AN: 53338

Middle Eastern (MID) AF: 0.0326 AC: 188 AN: 5768

European-Non Finnish (NFE) AF: 0.0233 AC: 25909 AN: 1111648

Other (OTH) AF: 0.0368 AC: 2220 AN: 60356

GnomAD4 genome AF: 0.0554 AC: 8439 AN: 152258 Hom.: 455 Cov.: 32 AF XY: 0.0538 AC XY: 4006 AN XY: 74456

African (AFR) AF: 0.135 AC: 5609 AN: 41538

American (AMR) AF: 0.0522 AC: 798 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0685 AC: 238 AN: 3472

East Asian (EAS) AF: 0.00773 AC: 40 AN: 5172

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4820

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0211 AC: 1433 AN: 68034

Other (OTH) AF: 0.0610 AC: 129 AN: 2114

Alfa AF: 0.0249 Hom.: 30

Bravo AF: 0.0632

Asia WGS AF: 0.0540 AC: 188 AN: 3478

EpiCase AF: 0.0254

EpiControl AF: 0.0255

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	-0.56
CADD	Benign	7.0
DANN	Benign	0.79
PhyloP100		1.1
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: rs35998713; hg19: chr8-106814695;