chr8-105801037-GTC-G

Variant names:

• chr8-105801037-GTC-G
• rs147661076
• NM_012082.4:c.965-4_965-3delCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_012082.4(ZFPM2):​c.965-4_965-3delCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,596,266 control chromosomes in the GnomAD database, including 20 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (6 hom.)
• Consequence: ZFPM2 NM_012082.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.47
• Publications: 0 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 -16 ACMG points.

• BP6: Variant 8-105801037-GTC-G is Benign according to our data. Variant chr8-105801037-GTC-G is described in ClinVar as Benign. ClinVar VariationId is 414004.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 = 0.00792 (1205/152200) while in subpopulation AFR AF = 0.0266 (1103/41536). AF 95% confidence interval is 0.0253. There are 14 homozygotes in GnomAd4. There are 564 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1205 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	NM_012082.4	MANE Select	c.965-4_965-3delCT		splice_region intron	N/A	NP_036214.2
	ZFPM2	NM_001362836.2		c.806-4_806-3delCT		splice_region intron	N/A	NP_001349765.1
	ZFPM2	NM_001362837.2		c.569-4_569-3delCT		splice_region intron	N/A	NP_001349766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.965-4_965-3delCT		splice_region intron	N/A	ENSP00000384179.2
	ZFPM2	ENST00000517361.1	TSL:2	c.569-4_569-3delCT		splice_region intron	N/A	ENSP00000428720.1
	ZFPM2	ENST00000520492.5	TSL:2	c.569-4_569-3delCT		splice_region intron	N/A	ENSP00000430757.1

Frequencies

GnomAD3 genomes AF: 0.00792 AC: 1204 AN: 152082 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00213 AC: 514 AN: 241426 AF XY: 0.00162

Gnomad AFR exome AF: 0.0273

Gnomad AMR exome AF: 0.00222

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000146

Gnomad OTH exome AF: 0.000347

GnomAD4 exome AF: 0.000853 AC: 1232 AN: 1444066 Hom.: 6 AF XY: 0.000773 AC XY: 553 AN XY: 715722

African (AFR) AF: 0.0271 AC: 892 AN: 32910

American (AMR) AF: 0.00213 AC: 92 AN: 43148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25266

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.0000709 AC: 6 AN: 84584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52994

Middle Eastern (MID) AF: 0.00159 AC: 9 AN: 5650

European-Non Finnish (NFE) AF: 0.000107 AC: 118 AN: 1100662

Other (OTH) AF: 0.00193 AC: 115 AN: 59476

GnomAD4 genome AF: 0.00792 AC: 1205 AN: 152200 Hom.: 14 Cov.: 32 AF XY: 0.00758 AC XY: 564 AN XY: 74398

African (AFR) AF: 0.0266 AC: 1103 AN: 41536

American (AMR) AF: 0.00464 AC: 71 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68012

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00386 Hom.: 0

Bravo AF: 0.00926

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Dec 03, 2021

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

46,XY sex reversal 9 Benign:1

Nov 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147661076; hg19: chr8-106813265;