2-227710291-C-T

Position:

• chr2-227710291-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025243.4(SLC19A3):​c.-3+7652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,014 control chromosomes in the GnomAD database, including 15,183 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (15183 hom., cov: 32)
• Consequence: SLC19A3 NM_025243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A3	NM_025243.4	c.-3+7652G>A		intron_variant		ENST00000644224.2	NP_079519.1
SLC19A3	NM_001371411.1	c.-3+4158G>A		intron_variant			NP_001358340.1
SLC19A3	NM_001371413.1	c.-211+7652G>A		intron_variant			NP_001358342.1
SLC19A3	XM_047445927.1	c.-395-3548G>A		intron_variant			XP_047301883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A3	ENST00000644224.2	c.-3+7652G>A		intron_variant			NM_025243.4	ENSP00000495385	P1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63747 AN: 151896 Hom.: 15188 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.485

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.419 AC: 63739 AN: 152014 Hom.: 15183 Cov.: 32 AF XY: 0.412 AC XY: 30593 AN XY: 74292

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.480

Alfa AF: 0.503 Hom.: 8558

Bravo AF: 0.410

Asia WGS AF: 0.236 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs13007334; hg19: chr2-228575007;