rs151229044

chr20-765436-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS1

The NM_033409.4(SLC52A3):c.339C>T(p.Phe113=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00111 in 1,613,158 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00076 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 4.20

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 20-765436-G-A is Benign according to our data. Variant chr20-765436-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 543063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-765436-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000762 (116/152324) while in subpopulation SAS AF= 0.00352 (17/4826). AF 95% confidence interval is 0.00224. There are 1 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC52A3	NM_033409.4	c.339C>T	p.Phe113=	synonymous_variant	2/5	ENST00000645534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC52A3	ENST00000645534.1	c.339C>T	p.Phe113=	synonymous_variant	2/5		NM_033409.4	P1

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 116 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00105 AC: 260 AN: 247002 Hom.: 1 AF XY: 0.00130 AC XY: 174 AN XY: 133632

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000644

Gnomad ASJ exome AF: 0.000501

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00310

Gnomad FIN exome AF: 0.0000949

Gnomad NFE exome AF: 0.00116

Gnomad OTH exome AF: 0.000994

GnomAD4 exome AF: 0.00115 AC: 1677 AN: 1460834 Hom.: 2 Cov.: 32 AF XY: 0.00119 AC XY: 865 AN XY: 726610

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000809

Gnomad4 ASJ exome AF: 0.000498

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00309

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.00111

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.000762 AC: 116 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000698 AC XY: 52 AN XY: 74484

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00113 Hom.: 0

Bravo AF: 0.000805

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	SLC52A3: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 08, 2020	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

p.Phe113Phe in exon 2 of SLC52A3: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.37% (56/15284) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs151229044). -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

SLC52A3-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 21, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Brown-Vialetto-van Laere syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	11
Dann	Benign	0.70

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: rs151229044; hg19: chr20-746080;