2-227696095-T-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_025243.4(SLC19A3):c.980-14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
SLC19A3
NM_025243.4 intron
NM_025243.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.746
Publications
9 publications found
Genes affected
SLC19A3 (HGNC:16266): (solute carrier family 19 member 3) This gene encodes a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity. Mutations in this gene cause biotin-responsive basal ganglia disease (BBGD); a recessive disorder manifested in childhood that progresses to chronic encephalopathy, dystonia, quadriparesis, and death if untreated. Patients with BBGD have bilateral necrosis in the head of the caudate nucleus and in the putamen. Administration of high doses of biotin in the early progression of the disorder eliminates pathological symptoms while delayed treatment results in residual paraparesis, mild cognitive disability, or dystonia. Administration of thiamine is ineffective in the treatment of this disorder. Experiments have failed to show that this protein can transport biotin. Mutations in this gene also cause a Wernicke's-like encephalopathy.[provided by RefSeq, Jan 2010]
SLC19A3 Gene-Disease associations (from GenCC):
- biotin-responsive basal ganglia diseaseInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
- Leigh syndromeInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- infantile spams-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Leigh syndrome with leukodystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- thiamine-responsive encephalopathyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 2-227696095-T-A is Benign according to our data. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-227696095-T-A is described in CliVar as Likely_benign. Clinvar id is 2905252.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000120 AC: 3AN: 250410 AF XY: 0.00000738 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
250410
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461250Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 726952 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461250
Hom.:
Cov.:
34
AF XY:
AC XY:
2
AN XY:
726952
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33460
American (AMR)
AF:
AC:
3
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39692
South Asian (SAS)
AF:
AC:
0
AN:
86236
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111462
Other (OTH)
AF:
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Biotin-responsive basal ganglia disease Benign:1
Oct 30, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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.