rs6054605

chr20-763926-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.645C>T(p.Pro215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,613,664 control chromosomes in the GnomAD database, including 6,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (734 hom., cov: 32)
  • Exomes 𝑓: 0.064 (5777 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.72

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=-0.89).
• BP6: Variant 20-763926-G-A is Benign according to our data. Variant chr20-763926-G-A is described in ClinVar as [Benign]. Clinvar id is 262237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763926-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-4.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC52A3	NM_033409.4	c.645C>T	p.Pro215=	synonymous_variant	3/5	ENST00000645534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC52A3	ENST00000645534.1	c.645C>T	p.Pro215=	synonymous_variant	3/5		NM_033409.4	P1

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10181 AN: 152024 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.0834

GnomAD3 exomes AF: 0.0854 AC: 21331 AN: 249854 Hom.: 2460 AF XY: 0.0829 AC XY: 11207 AN XY: 135198

Gnomad AFR exome AF: 0.0496

Gnomad AMR exome AF: 0.0600

Gnomad ASJ exome AF: 0.0669

Gnomad EAS exome AF: 0.467

Gnomad SAS exome AF: 0.0544

Gnomad FIN exome AF: 0.0271

Gnomad NFE exome AF: 0.0577

Gnomad OTH exome AF: 0.0803

GnomAD4 exome AF: 0.0637 AC: 93128 AN: 1461522 Hom.: 5777 Cov.: 64 AF XY: 0.0635 AC XY: 46187 AN XY: 727016

Gnomad4 AFR exome AF: 0.0465

Gnomad4 AMR exome AF: 0.0592

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.0548

Gnomad4 FIN exome AF: 0.0285

Gnomad4 NFE exome AF: 0.0537

Gnomad4 OTH exome AF: 0.0849

GnomAD4 genome AF: 0.0669 AC: 10183 AN: 152142 Hom.: 734 Cov.: 32 AF XY: 0.0689 AC XY: 5126 AN XY: 74380

Gnomad4 AFR AF: 0.0473

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.0718

Gnomad4 FIN AF: 0.0249

Gnomad4 NFE AF: 0.0544

Gnomad4 OTH AF: 0.0830

Alfa AF: 0.0637 Hom.: 861

Bravo AF: 0.0729

Asia WGS AF: 0.195 AC: 675 AN: 3478

EpiCase AF: 0.0630

EpiControl AF: 0.0667

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Pro215Pro 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 46.21% (3846/8322) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs6054605). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Brown-Vialetto-van Laere syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.43
Dann	Benign	0.63

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: rs6054605; hg19: chr20-744570; COSMIC: COSV54077373;