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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.746

Publications

9 publications found

Variant links:

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 disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
Leigh syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
infantile spams-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome with leukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
thiamine-responsive encephalopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC19A3 links:

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

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A3	NM_025243.4 link	c.980-14A>T		intron_variant	Intron 3 of 5	ENST00000644224.2	NP_079519.1	Q9BZV2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A3	ENST00000644224.2 link	c.980-14A>T		intron_variant	Intron 3 of 5		NM_025243.4	ENSP00000495385.1		Q9BZV2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250410

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000874

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461250

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.0000671

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111462

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.22

(source)

DANN

Benign

0.63

PhyloP100

-0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over