chr20-763806-G-A

Position:

• chr20-763806-G-A

Variant summary

Our verdict is Benign. Variant got -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 (★★).

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 262238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763806-G-A is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC52A3	NM_033409.4	c.765C>T	p.Leu255Leu	synonymous_variant	3/5	ENST00000645534.1	NP_212134.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000645534.1	c.765C>T	p.Leu255Leu	synonymous_variant	3/5		NM_033409.4	ENSP00000494193.1

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

GnomAD3 exomes AF: 0.436 AC: 109490 AN: 251316 Hom.: 25646 AF XY: 0.442 AC XY: 60010 AN XY: 135836

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 SAS exome AF: 0.478

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

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.483

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.433

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

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.396

Alfa AF: 0.447 Hom.: 20387

Bravo AF: 0.365

Asia WGS AF: 0.289 AC: 1007 AN: 3478

EpiCase AF: 0.473

EpiControl AF: 0.467

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Leu255Leu in exon 3 of SLC52A3: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 53.54% (6191/11564 ) of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs3746805). -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Brown-Vialetto-van Laere syndrome 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Progressive bulbar palsy of childhood Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.2
DANN	Benign	0.50

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