rs16873741

Variant names:

• chr8-105803246-C-T
• rs16873741
• NM_012082.4:c.3164C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-105803246-C-T
• chr8-105803246-C-A

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.3164C>T​(p.Ala1055Val) variant causes a missense change. The variant allele was found at a frequency of 0.0107 in 1,604,796 control chromosomes in the GnomAD database, including 1,516 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 0.057 (796 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (720 hom.)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.08
• Publications: 13 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=0.0015640557).
• BP6: Variant 8-105803246-C-T is Benign according to our data. Variant chr8-105803246-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 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.3164C>T	p.Ala1055Val	missense	Exon 8 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.3005C>T	p.Ala1002Val	missense	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.2768C>T	p.Ala923Val	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.3164C>T	p.Ala1055Val	missense	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.3161C>T	p.Ala1054Val	missense	Exon 8 of 8	ENSP00000611435.1
	ZFPM2	ENST00000517361.1	TSL:2	c.2768C>T	p.Ala923Val	missense	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8652 AN: 152076 Hom.: 792 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0149 AC: 3615 AN: 242884 AF XY: 0.0113

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.00106

Gnomad EAS exome AF: 0.0000561

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000569

Gnomad OTH exome AF: 0.00738

GnomAD4 exome AF: 0.00589 AC: 8556 AN: 1452602 Hom.: 720 Cov.: 32 AF XY: 0.00510 AC XY: 3679 AN XY: 721468

African (AFR) AF: 0.198 AC: 6566 AN: 33102

American (AMR) AF: 0.0127 AC: 556 AN: 43840

Ashkenazi Jewish (ASJ) AF: 0.00101 AC: 26 AN: 25616

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39544

South Asian (SAS) AF: 0.000506 AC: 43 AN: 85020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53146

Middle Eastern (MID) AF: 0.0109 AC: 62 AN: 5704

European-Non Finnish (NFE) AF: 0.000419 AC: 464 AN: 1106724

Other (OTH) AF: 0.0140 AC: 838 AN: 59906

GnomAD4 genome AF: 0.0571 AC: 8686 AN: 152194 Hom.: 796 Cov.: 32 AF XY: 0.0547 AC XY: 4067 AN XY: 74404

African (AFR) AF: 0.196 AC: 8144 AN: 41488

American (AMR) AF: 0.0263 AC: 402 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68020

Other (OTH) AF: 0.0350 AC: 74 AN: 2112

Alfa AF: 0.0216 Hom.: 940

Bravo AF: 0.0647

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.173 AC: 685

ESP6500EA AF: 0.000720 AC: 6

ExAC AF: 0.0173 AC: 2095

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Benign	0.24	T
Sift4G	Benign	0.19	T
Polyphen		0.020	B
Vest4		0.17
MPC		0.11
ClinPred		0.033	T
GERP RS		6.0
Varity_R		0.054
gMVP		0.33
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: rs16873741; hg19: chr8-106815474;