chr20-761203-A-G

Position:

• chr20-761203-A-G

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.1233T>C​(p.Ser411Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,558,282 control chromosomes in the GnomAD database, including 397,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35962 hom., cov: 35)
  • Exomes 𝑓: 0.72 (361991 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.24

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=-0.51).
• BP6: Variant 20-761203-A-G is Benign according to our data. Variant chr20-761203-A-G is described in ClinVar as [Benign]. Clinvar id is 262230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-761203-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC52A3	NM_033409.4	c.1233T>C	p.Ser411Ser	synonymous_variant	5/5	ENST00000645534.1	NP_212134.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000645534.1	c.1233T>C	p.Ser411Ser	synonymous_variant	5/5		NM_033409.4	ENSP00000494193.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104196 AN: 152114 Hom.: 35935 Cov.: 35

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.678

GnomAD3 exomes AF: 0.681 AC: 112365 AN: 165046 Hom.: 38694 AF XY: 0.687 AC XY: 61139 AN XY: 88944

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.706

Gnomad EAS exome AF: 0.525

Gnomad SAS exome AF: 0.730

Gnomad FIN exome AF: 0.733

Gnomad NFE exome AF: 0.715

Gnomad OTH exome AF: 0.683

GnomAD4 exome AF: 0.716 AC: 1006058 AN: 1406048 Hom.: 361991 Cov.: 77 AF XY: 0.717 AC XY: 497785 AN XY: 694290

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.608

Gnomad4 ASJ exome AF: 0.703

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.732

Gnomad4 FIN exome AF: 0.737

Gnomad4 NFE exome AF: 0.729

Gnomad4 OTH exome AF: 0.708

GnomAD4 genome AF: 0.685 AC: 104278 AN: 152234 Hom.: 35962 Cov.: 35 AF XY: 0.685 AC XY: 50974 AN XY: 74444

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.677

Alfa AF: 0.687 Hom.: 9848

Bravo AF: 0.673

Asia WGS AF: 0.609 AC: 2118 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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	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.Ser411Ser in exon 5 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 73.41% (6372/8680) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs910857). -

not provided Benign:2

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

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	-0.51
CADD	Benign	12
DANN	Benign	0.73

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: rs910857; hg19: chr20-741847; COSMIC: COSV54077188;