rs35843564

Variant names:

• chr8-105801358-G-A
• rs35843564
• NM_012082.4:c.1276G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-105801358-G-A
• chr8-105801358-G-C
• chr8-105801358-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012082.4(ZFPM2):​c.1276G>A​(p.Ala426Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000693 in 1,613,880 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (2 hom.)
• Consequence: ZFPM2 NM_012082.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.290
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024237037).
• BP6: Variant 8-105801358-G-A is Benign according to our data. Variant chr8-105801358-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 544225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00276 (420/152206) while in subpopulation AFR AF = 0.0093 (386/41522). AF 95% confidence interval is 0.00853. There are 1 homozygotes in GnomAd4. There are 187 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 420 AD,Unknown gene.

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.1276G>A	p.Ala426Thr	missense	Exon 8 of 8	NP_036214.2	Q8WW38-1
	ZFPM2	NM_001362836.2		c.1117G>A	p.Ala373Thr	missense	Exon 7 of 7	NP_001349765.1
	ZFPM2	NM_001362837.2		c.880G>A	p.Ala294Thr	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.1276G>A	p.Ala426Thr	missense	Exon 8 of 8	ENSP00000384179.2	Q8WW38-1
	ZFPM2	ENST00000941376.1		c.1273G>A	p.Ala425Thr	missense	Exon 8 of 8	ENSP00000611435.1
	ZFPM2	ENST00000517361.1	TSL:2	c.880G>A	p.Ala294Thr	missense	Exon 6 of 6	ENSP00000428720.1	E7ET52

Frequencies

GnomAD3 genomes AF: 0.00277 AC: 422 AN: 152088 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00110 AC: 273 AN: 248830 AF XY: 0.000933

Gnomad AFR exome AF: 0.00911

Gnomad AMR exome AF: 0.000783

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00151

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000994

GnomAD4 exome AF: 0.000478 AC: 699 AN: 1461674 Hom.: 2 Cov.: 31 AF XY: 0.000485 AC XY: 353 AN XY: 727118

African (AFR) AF: 0.00959 AC: 321 AN: 33480

American (AMR) AF: 0.000895 AC: 40 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00154 AC: 61 AN: 39690

South Asian (SAS) AF: 0.00194 AC: 167 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111856

Other (OTH) AF: 0.00131 AC: 79 AN: 60374

GnomAD4 genome AF: 0.00276 AC: 420 AN: 152206 Hom.: 1 Cov.: 32 AF XY: 0.00251 AC XY: 187 AN XY: 74414

African (AFR) AF: 0.00930 AC: 386 AN: 41522

American (AMR) AF: 0.000917 AC: 14 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5174

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000977 Hom.: 1

Bravo AF: 0.00312

ESP6500AA AF: 0.00867 AC: 34

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00144 AC: 174

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.065
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.82
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.29
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.045
Sift	Benign	0.43	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.043
MVP		0.12
MPC		0.094
ClinPred		0.0027	T
GERP RS		1.1
Varity_R		0.035
gMVP		0.20
Mutation Taster		=86/14	polymorphism

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: rs35843564; hg19: chr8-106813586;