rs730880271
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016180.5(SLC45A2):c.1121delT(p.Leu374CysfsTer24) variant causes a frameshift 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SLC45A2
NM_016180.5 frameshift
NM_016180.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.03
Publications
2 publications found
Genes affected
SLC45A2 (HGNC:16472): (solute carrier family 45 member 2) This gene encodes a transporter protein that mediates melanin synthesis. The protein is expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
SLC45A2 Gene-Disease associations (from GenCC):
- oculocutaneous albinism type 4Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia
Genome browser will be placed here
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 5-33951588-CA-C is Pathogenic according to our data. Variant chr5-33951588-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 4506.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_016180.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| SLC45A2 | MANE Select | c.1121delT | p.Leu374CysfsTer24 | frameshift | Exon 5 of 7 | NP_057264.4 | |||
| SLC45A2 | c.1121delT | p.Leu374CysfsTer24 | frameshift | Exon 5 of 6 | NP_001012527.2 | Q9UMX9-4 | |||
| SLC45A2 | c.*63delT | 3_prime_UTR | Exon 4 of 4 | NP_001284346.2 | D6RGY6 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC45A2 | TSL:1 MANE Select | c.1121delT | p.Leu374CysfsTer24 | frameshift | Exon 5 of 7 | ENSP00000296589.4 | Q9UMX9-1 | ||
| SLC45A2 | TSL:1 | c.1121delT | p.Leu374CysfsTer24 | frameshift | Exon 5 of 6 | ENSP00000371534.3 | Q9UMX9-4 | ||
| SLC45A2 | TSL:1 | c.*63delT | 3_prime_UTR | Exon 4 of 4 | ENSP00000421100.1 | D6RGY6 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461858Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 727234 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1461858
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
727234
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111994
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
1
-
-
Oculocutaneous albinism type 4 (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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.