1-100896280-C-CA
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_133496.5(SLC30A7):c.21dupA(p.Asp8fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
SLC30A7
NM_133496.5 frameshift
NM_133496.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.87
Genes affected
SLC30A7 (HGNC:19306): (solute carrier family 30 member 7) Zinc functions as a cofactor for numerous enzymes, nuclear factors, and hormones and as an intra- and intercellular signal ion. Members of the zinc transporter (ZNT)/SLC30 subfamily of the cation diffusion facilitator family, such as SLC30A7, permit cellular efflux of zinc (Seve et al., 2004 [PubMed 15154973]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-100896280-C-CA is Pathogenic according to our data. Variant chr1-100896280-C-CA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1711192.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC30A7 | NM_133496.5 | c.21dupA | p.Asp8fs | frameshift_variant | 1/11 | ENST00000357650.9 | NP_598003.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC30A7 | ENST00000357650.9 | c.21dupA | p.Asp8fs | frameshift_variant | 1/11 | 1 | NM_133496.5 | ENSP00000350278.4 | ||
SLC30A7 | ENST00000370112.8 | c.21dupA | p.Asp8fs | frameshift_variant | 1/12 | 1 | ENSP00000359130.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251484Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135920
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727246
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ziegler-Huang syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 08, 2024 | - - |
Decreased testicular size Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Department of Genetics, CHU d'Angers | Oct 11, 2022 | We identified these variants in 2 siblings presenting with the unusual combination of testicular hypoplasia, short stature and bone marrow failure. Decrease of protein level was confirmed by Western blot. The phenotype is similar to the one associated with TP53 (PMID 30146126) which is known to interact with ZNT7. BOth variants were shown to decrease the mRNA level. - |
Computational scores
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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