8-105444338-A-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_012082.4(ZFPM2):āc.258A>Gā(p.Lys86=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,612,456 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 (ā ā ).
Frequency
Genomes: š 0.00023 ( 0 hom., cov: 33)
Exomes š: 0.000026 ( 0 hom. )
Consequence
ZFPM2
NM_012082.4 synonymous
NM_012082.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.990
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 8-105444338-A-G is Benign according to our data. Variant chr8-105444338-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1168530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.99 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00023 (35/152288) while in subpopulation AFR AF= 0.00077 (32/41564). AF 95% confidence interval is 0.00056. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 35 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFPM2 | NM_012082.4 | c.258A>G | p.Lys86= | synonymous_variant | 3/8 | ENST00000407775.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFPM2 | ENST00000407775.7 | c.258A>G | p.Lys86= | synonymous_variant | 3/8 | 1 | NM_012082.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152170Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000649 AC: 16AN: 246498Hom.: 0 AF XY: 0.0000599 AC XY: 8AN XY: 133532
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GnomAD4 exome AF: 0.0000260 AC: 38AN: 1460168Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 20AN XY: 726066
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GnomAD4 genome AF: 0.000230 AC: 35AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
46,XY sex reversal 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2023 | - - |
ZFPM2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 15, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at