20-763806-G-A

Variant names:

• chr20-763806-G-A
• rs3746805
• NM_033409.4:c.765C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033409.4(SLC52A3):​c.765C>T​(p.Leu255Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,613,914 control chromosomes in the GnomAD database, including 170,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L255L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.38 (12638 hom., cov: 33)
  • Exomes 𝑓: 0.46 (158104 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.463
• Publications: 24 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=-0.53).
• BP6: Variant 20-763806-G-A is Benign according to our data. Variant chr20-763806-G-A is described in ClinVar as Benign. ClinVar VariationId is 262238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.463 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

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.765C>T	p.Leu255Leu	synonymous	Exon 3 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.765C>T	p.Leu255Leu	synonymous	Exon 4 of 6	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.765C>T	p.Leu255Leu	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.765C>T	p.Leu255Leu	synonymous	Exon 3 of 5	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000217254.11	TSL:5	c.765C>T	p.Leu255Leu	synonymous	Exon 4 of 6	ENSP00000217254.7	Q9NQ40-1
	SLC52A3	ENST00000488495.3	TSL:3	c.765C>T	p.Leu255Leu	synonymous	Exon 3 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57749 AN: 151950 Hom.: 12626 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.436 AC: 109490 AN: 251316 AF XY: 0.442

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.510

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.519

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.450

GnomAD4 exome AF: 0.459 AC: 670813 AN: 1461844 Hom.: 158104 Cov.: 82 AF XY: 0.460 AC XY: 334615 AN XY: 727220

African (AFR) AF: 0.173 AC: 5782 AN: 33478

American (AMR) AF: 0.504 AC: 22528 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 12593 AN: 26134

East Asian (EAS) AF: 0.139 AC: 5515 AN: 39700

South Asian (SAS) AF: 0.483 AC: 41626 AN: 86250

European-Finnish (FIN) AF: 0.515 AC: 27494 AN: 53408

Middle Eastern (MID) AF: 0.498 AC: 2873 AN: 5766

European-Non Finnish (NFE) AF: 0.473 AC: 526274 AN: 1111988

Other (OTH) AF: 0.433 AC: 26128 AN: 60396

GnomAD4 genome AF: 0.380 AC: 57768 AN: 152070 Hom.: 12638 Cov.: 33 AF XY: 0.381 AC XY: 28329 AN XY: 74332

African (AFR) AF: 0.177 AC: 7364 AN: 41508

American (AMR) AF: 0.416 AC: 6354 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3470

East Asian (EAS) AF: 0.143 AC: 739 AN: 5168

South Asian (SAS) AF: 0.477 AC: 2295 AN: 4810

European-Finnish (FIN) AF: 0.530 AC: 5610 AN: 10576

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32230 AN: 67944

Other (OTH) AF: 0.396 AC: 836 AN: 2110

Alfa AF: 0.439 Hom.: 24067

Bravo AF: 0.365

Asia WGS AF: 0.289 AC: 1007 AN: 3478

EpiCase AF: 0.473

EpiControl AF: 0.467

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Brown-Vialetto-van Laere syndrome 1 (2)
-	-	2	not provided (2)
-	-	1	Progressive bulbar palsy of childhood (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.46
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3746805; hg19: chr20-744450; COSMIC: COSV54077519;