rs3746807

Variant names:

• chr20-765319-G-A
• rs3746807
• NM_033409.4:c.456C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-765319-G-A
• chr20-765319-G-T

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.456C>T​(p.Pro152Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,613,980 control chromosomes in the GnomAD database, including 9,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (806 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8773 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.14

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=-0.48).
• BP6: Variant 20-765319-G-A is Benign according to our data. Variant chr20-765319-G-A is described in ClinVar as [Benign]. Clinvar id is 262234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-765319-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4	c.456C>T	p.Pro152Pro	synonymous_variant	Exon 2 of 5	ENST00000645534.1	NP_212134.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000645534.1	c.456C>T	p.Pro152Pro	synonymous_variant	Exon 2 of 5		NM_033409.4	ENSP00000494193.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15334 AN: 152016 Hom.: 805 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0917

GnomAD3 exomes AF: 0.0957 AC: 24062 AN: 251434 Hom.: 1344 AF XY: 0.0941 AC XY: 12794 AN XY: 135910

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.0544

Gnomad ASJ exome AF: 0.0575

Gnomad EAS exome AF: 0.177

Gnomad SAS exome AF: 0.0655

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.0908

GnomAD4 exome AF: 0.106 AC: 154446 AN: 1461846 Hom.: 8773 Cov.: 33 AF XY: 0.105 AC XY: 76092 AN XY: 727228

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0566

Gnomad4 ASJ exome AF: 0.0562

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.0652

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.0995

GnomAD4 genome AF: 0.101 AC: 15363 AN: 152134 Hom.: 806 Cov.: 32 AF XY: 0.0998 AC XY: 7425 AN XY: 74368

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0836

Gnomad4 ASJ AF: 0.0505

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.0521

Gnomad4 FIN AF: 0.0983

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0907

Alfa AF: 0.0992 Hom.: 1854

Bravo AF: 0.102

Asia WGS AF: 0.125 AC: 436 AN: 3478

EpiCase AF: 0.0961

EpiControl AF: 0.0962

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Pro152Pro in exon 2 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 18.19% (1570/8630) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs3746807). -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Brown-Vialetto-van Laere syndrome 1 Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.3
DANN	Benign	0.75

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: rs3746807; hg19: chr20-745963; COSMIC: COSV54077450;