rs281860288
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018713.3(SLC30A10):c.585delG(p.Thr196ProfsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SLC30A10
NM_018713.3 frameshift
NM_018713.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0440
Publications
2 publications found
Genes affected
SLC30A10 (HGNC:25355): (solute carrier family 30 member 10) This gene is highly expressed in the liver and is inducible by manganese. Its protein product appears to be critical in maintaining manganese levels, and has higher specificity for manganese than zinc. Loss of function mutations appear to result in a pleomorphic phenotype, including dystonia and adult-onset parkinsonism. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]
SLC30A10 Gene-Disease associations (from GenCC):
- cirrhosis - dystonia - polycythemia - hypermanganesemia syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-219927855-TC-T is Pathogenic according to our data. Variant chr1-219927855-TC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 30887.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018713.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC30A10 | NM_018713.3 | MANE Select | c.585delG | p.Thr196ProfsTer17 | frameshift | Exon 1 of 4 | NP_061183.2 | ||
| SLC30A10 | NM_001416005.1 | c.-129delG | 5_prime_UTR | Exon 1 of 4 | NP_001402934.1 | B3KR19 | |||
| SLC30A10 | NM_001376929.1 | c.452-751delG | intron | N/A | NP_001363858.1 | A0A8Q3WLF3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC30A10 | ENST00000366926.4 | TSL:1 MANE Select | c.585delG | p.Thr196ProfsTer17 | frameshift | Exon 1 of 4 | ENSP00000355893.4 | Q6XR72-4 | |
| SLC30A10 | ENST00000356609.2 | TSL:1 | n.585delG | non_coding_transcript_exon | Exon 1 of 4 | ENSP00000349018.2 | Q6XR72-3 | ||
| SLC30A10 | ENST00000886495.1 | c.585delG | p.Thr196ProfsTer17 | frameshift | Exon 1 of 4 | ENSP00000556554.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1393488Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 688056
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1393488
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
688056
African (AFR)
AF:
AC:
0
AN:
29404
American (AMR)
AF:
AC:
0
AN:
35642
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24766
East Asian (EAS)
AF:
AC:
0
AN:
33988
South Asian (SAS)
AF:
AC:
0
AN:
79008
European-Finnish (FIN)
AF:
AC:
0
AN:
49286
Middle Eastern (MID)
AF:
AC:
0
AN:
5636
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1078094
Other (OTH)
AF:
AC:
0
AN:
57664
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Hypermanganesemia with dystonia, polycythemia, and cirrhosis (2)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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