rs1131692331
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4_SupportingPP5_Moderate
The NM_006345.4(SLC30A9):c.1049_1051delCAG(p.Ala350del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SLC30A9
NM_006345.4 disruptive_inframe_deletion
NM_006345.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.79
Genes affected
SLC30A9 (HGNC:1329): (solute carrier family 30 member 9) Predicted to enable nuclear receptor coactivator activity. Involved in cellular zinc ion homeostasis and zinc ion transport. Located in several cellular components, including cytoplasmic vesicle; cytoskeleton; and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_006345.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 4-42065323-TAGC-T is Pathogenic according to our data. Variant chr4-42065323-TAGC-T is described in ClinVar as [Pathogenic]. Clinvar id is 431049.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC30A9 | NM_006345.4 | c.1049_1051delCAG | p.Ala350del | disruptive_inframe_deletion | 12/18 | ENST00000264451.12 | NP_006336.3 | |
SLC30A9 | XM_047449525.1 | c.1049_1051delCAG | p.Ala350del | disruptive_inframe_deletion | 12/13 | XP_047305481.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC30A9 | ENST00000264451.12 | c.1049_1051delCAG | p.Ala350del | disruptive_inframe_deletion | 12/18 | 1 | NM_006345.4 | ENSP00000264451.6 | ||
SLC30A9 | ENST00000509683.5 | n.105_107delCAG | non_coding_transcript_exon_variant | 2/6 | 3 | |||||
SLC30A9 | ENST00000513699.5 | n.*806_*808delCAG | non_coding_transcript_exon_variant | 13/19 | 2 | ENSP00000423529.1 | ||||
SLC30A9 | ENST00000513699.5 | n.*806_*808delCAG | 3_prime_UTR_variant | 13/19 | 2 | ENSP00000423529.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | May 04, 2022 | - - |
Pathogenic, criteria provided, single submitter | research | UAEU Genomics Laboratory, United Arab Emirates University | Apr 08, 2023 | The in-frame deletion NM_006345.4(SLC30A9):c.1049_1051delCAG (p.Ala350del) has been reported previously in 6 individuals from a Bedouin kindred affected with Birk-Landau-Perez syndrome (Perez et al., 2017). This variant is not present in gnomAD database (Karczewski et al., 2020) and Middle Eastern specific databases (Koshy et al., 2017). The removed amino acid is highly conserved and is located at the predicted cation-efflux domain of the mature SLC30A9 protein. In vitro functional studies in human neuroblastoma cells showed a significant decrease in cytosolic free Zn2+ levels in cells expressing the mutant compared to the wild type. (Perez et al., 2017).Further, in CRISPR-Cas9 knockout (SLC30A9 -/-) cell lines, functional complementation of the p.Ala350Del variant failed to restore the functional defect caused by genetic ablation of SLC30A9, indicating that the p.Ala350Del variant is a loss-of-function allele (Deng et al., 2021). Aggregating all the available evidence (PM2, PM1, PS3, PP1_strong), this variant has been classified as Pathogenic. - |
Computational scores
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Calibrated prediction
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Prediction
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