rs3746806

Variant names:

• chr20-763866-G-A
• rs3746806
• NM_033409.4:c.705C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-763866-G-A
• chr20-763866-G-C
• chr20-763866-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_033409.4(SLC52A3):​c.705C>T​(p.Leu235Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,614,156 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L235L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0097 (15 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (14 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.562
• Publications: 1 publications found

Genes affected

SLC52A3 (HGNC:16187): (solute carrier family 52 member 3) This gene encodes a riboflavin transporter protein that is strongly expressed in the intestine and likely plays a role in intestinal absorption of riboflavin. The protein is predicted to have eleven transmembrane domains and a cell surface localization signal in the C-terminus. Mutations at this locus have been associated with Brown-Vialetto-Van Laere syndrome and Fazio-Londe disease. [provided by RefSeq, Mar 2012]

SLC52A3 Gene-Disease associations (from GenCC):

• Brown-Vialetto-van Laere syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, PanelApp Australia, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• progressive bulbar palsy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 20-763866-G-A is Benign according to our data. Variant chr20-763866-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.562 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00965 (1470/152266) while in subpopulation AFR AF = 0.0333 (1385/41548). AF 95% confidence interval is 0.0319. There are 15 homozygotes in GnomAd4. There are 688 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033409.4. 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
	SLC52A3	NM_033409.4	MANE Select	c.705C>T	p.Leu235Leu	synonymous	Exon 3 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.705C>T	p.Leu235Leu	synonymous	Exon 4 of 6	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.705C>T	p.Leu235Leu	synonymous	Exon 4 of 6	NP_001357015.1	Q9NQ40-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	ENST00000645534.1	MANE Select	c.705C>T	p.Leu235Leu	synonymous	Exon 3 of 5	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000217254.11	TSL:5	c.705C>T	p.Leu235Leu	synonymous	Exon 4 of 6	ENSP00000217254.7	Q9NQ40-1
	SLC52A3	ENST00000488495.3	TSL:3	c.705C>T	p.Leu235Leu	synonymous	Exon 3 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.00960 AC: 1460 AN: 152148 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00273 AC: 687 AN: 251366 AF XY: 0.00199

Gnomad AFR exome AF: 0.0375

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00102 AC: 1485 AN: 1461890 Hom.: 14 Cov.: 63 AF XY: 0.000891 AC XY: 648 AN XY: 727244

African (AFR) AF: 0.0357 AC: 1195 AN: 33480

American (AMR) AF: 0.00174 AC: 78 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1112010

Other (OTH) AF: 0.00215 AC: 130 AN: 60396

GnomAD4 genome AF: 0.00965 AC: 1470 AN: 152266 Hom.: 15 Cov.: 32 AF XY: 0.00924 AC XY: 688 AN XY: 74440

African (AFR) AF: 0.0333 AC: 1385 AN: 41548

American (AMR) AF: 0.00340 AC: 52 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68012

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00368 Hom.: 3

Bravo AF: 0.0111

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Brown-Vialetto-van Laere syndrome 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.7
DANN	Benign	0.56
PhyloP100		0.56
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3746806; hg19: chr20-744510;