rs117908591
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_012082.4(ZFPM2):c.2287G>A(p.Val763Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00416 in 1,613,702 control chromosomes in the GnomAD database, including 18 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 0.0032 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0043 ( 17 hom. )
Consequence
ZFPM2
NM_012082.4 missense
NM_012082.4 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.16
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.004432678).
BP6
?
Variant 8-105802369-G-A is Benign according to our data. Variant chr8-105802369-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-105802369-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00322 (490/152238) while in subpopulation NFE AF= 0.00497 (338/68020). AF 95% confidence interval is 0.00453. There are 1 homozygotes in gnomad4. There are 235 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 490 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFPM2 | NM_012082.4 | c.2287G>A | p.Val763Ile | missense_variant | 8/8 | ENST00000407775.7 | |
ZFPM2-AS1 | NR_125797.1 | n.191-3927C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFPM2 | ENST00000407775.7 | c.2287G>A | p.Val763Ile | missense_variant | 8/8 | 1 | NM_012082.4 | P1 | |
ZFPM2-AS1 | ENST00000520433.5 | n.212-3927C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00322 AC: 490AN: 152120Hom.: 1 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00266 AC: 656AN: 247080Hom.: 3 AF XY: 0.00271 AC XY: 364AN XY: 134132
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GnomAD4 exome AF: 0.00426 AC: 6230AN: 1461464Hom.: 17 Cov.: 31 AF XY: 0.00420 AC XY: 3052AN XY: 727012
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GnomAD4 genome ? AF: 0.00322 AC: 490AN: 152238Hom.: 1 Cov.: 32 AF XY: 0.00316 AC XY: 235AN XY: 74438
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26
ESP6500AA
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3
ESP6500EA
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37
ExAC
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294
Asia WGS
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | ZFPM2: BP4, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 08, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
46,XY sex reversal 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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