rs11993776

Variant names:

• chr8-105801290-C-G
• rs11993776
• NM_012082.4:c.1208C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-105801290-C-G
• chr8-105801290-C-T

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.1208C>G​(p.Ala403Gly) variant causes a missense change. The variant allele was found at a frequency of 0.109 in 1,613,686 control chromosomes in the GnomAD database, including 13,171 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3722 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9449 hom.)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.12
• Publications: 22 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=0.0036206841).
• BP6: Variant 8-105801290-C-G is Benign according to our data. Variant chr8-105801290-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 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.1208C>G	p.Ala403Gly	missense	Exon 8 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.1049C>G	p.Ala350Gly	missense	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.812C>G	p.Ala271Gly	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.1208C>G	p.Ala403Gly	missense	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.1205C>G	p.Ala402Gly	missense	Exon 8 of 8	ENSP00000611435.1
	ZFPM2	ENST00000517361.1	TSL:2	c.812C>G	p.Ala271Gly	missense	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26745 AN: 151892 Hom.: 3699 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0685

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.110 AC: 27377 AN: 249044 AF XY: 0.105

Gnomad AFR exome AF: 0.394

Gnomad AMR exome AF: 0.0780

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.129

Gnomad FIN exome AF: 0.0799

Gnomad NFE exome AF: 0.0910

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.102 AC: 148490 AN: 1461676 Hom.: 9449 Cov.: 32 AF XY: 0.0996 AC XY: 72417 AN XY: 727120

African (AFR) AF: 0.393 AC: 13173 AN: 33480

American (AMR) AF: 0.0824 AC: 3686 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2941 AN: 26136

East Asian (EAS) AF: 0.163 AC: 6482 AN: 39696

South Asian (SAS) AF: 0.0778 AC: 6707 AN: 86258

European-Finnish (FIN) AF: 0.0806 AC: 4303 AN: 53398

Middle Eastern (MID) AF: 0.0843 AC: 486 AN: 5768

European-Non Finnish (NFE) AF: 0.0931 AC: 103543 AN: 1111848

Other (OTH) AF: 0.119 AC: 7169 AN: 60372

GnomAD4 genome AF: 0.176 AC: 26827 AN: 152010 Hom.: 3722 Cov.: 32 AF XY: 0.172 AC XY: 12758 AN XY: 74284

African (AFR) AF: 0.388 AC: 16053 AN: 41390

American (AMR) AF: 0.132 AC: 2010 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3470

East Asian (EAS) AF: 0.138 AC: 710 AN: 5158

South Asian (SAS) AF: 0.0682 AC: 328 AN: 4812

European-Finnish (FIN) AF: 0.0686 AC: 727 AN: 10600

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6209 AN: 67990

Other (OTH) AF: 0.164 AC: 347 AN: 2112

Alfa AF: 0.106 Hom.: 845

Bravo AF: 0.190

TwinsUK AF: 0.0984 AC: 365

ALSPAC AF: 0.0939 AC: 362

ESP6500AA AF: 0.357 AC: 1423

ESP6500EA AF: 0.0941 AC: 787

ExAC AF: 0.115 AC: 13842

Asia WGS AF: 0.145 AC: 505 AN: 3478

EpiCase AF: 0.0911

EpiControl AF: 0.0904

ClinVar

ClinVar submissions

Significance: Benign/Likely 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
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.72
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.9	N
PhyloP100		4.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	0.87	T
Polyphen		0.0	B
Vest4		0.019
MPC		0.097
ClinPred		0.0021	T
GERP RS		4.0
Varity_R		0.040
gMVP		0.25
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: rs11993776; hg19: chr8-106813518; COSMIC: COSV65873817;