8-105318992-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_012082.4(ZFPM2):​c.40+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,340,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

ZFPM2
NM_012082.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.39

Publications

0 publications found
Variant links:
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 Gene-Disease associations (from GenCC):
  • 46,XY sex reversal 9
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • diaphragmatic hernia 3
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • tetralogy of fallot
    Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • 46,XY partial gonadal dysgenesis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 8-105318992-G-C is Benign according to our data. Variant chr8-105318992-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2978007.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFPM2NM_012082.4 linkc.40+11G>C intron_variant Intron 1 of 7 ENST00000407775.7 NP_036214.2 Q8WW38-1Q9NPQ0
ZFPM2NM_001362836.2 linkc.40+11G>C intron_variant Intron 1 of 6 NP_001349765.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFPM2ENST00000407775.7 linkc.40+11G>C intron_variant Intron 1 of 7 1 NM_012082.4 ENSP00000384179.2 Q8WW38-1
ZFPM2ENST00000518180.1 linkn.479+72463G>C intron_variant Intron 4 of 4 4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000837
AC:
1
AN:
119420
AF XY:
0.0000155
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000224
AC:
3
AN:
1340112
Hom.:
0
Cov.:
31
AF XY:
0.00000302
AC XY:
2
AN XY:
661230
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28368
American (AMR)
AF:
0.00
AC:
0
AN:
31366
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23770
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30632
South Asian (SAS)
AF:
0.0000135
AC:
1
AN:
73872
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47028
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5106
European-Non Finnish (NFE)
AF:
9.57e-7
AC:
1
AN:
1045272
Other (OTH)
AF:
0.0000183
AC:
1
AN:
54698
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

46,XY sex reversal 9 Benign:1
Oct 06, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
16
DANN
Benign
0.92
PhyloP100
1.4

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

Publications

Other links and lift over

dbSNP: rs550883122; hg19: chr8-106331220; API