rs73576869

chr20-763477-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033409.4(SLC52A3):c.1073+21A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,613,696 control chromosomes in the GnomAD database, including 1,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (114 hom., cov: 33)
  • Exomes 𝑓: 0.013 (1047 hom.)
• Consequence: SLC52A3 NM_033409.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0890

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-763477-T-A is Benign according to our data. Variant chr20-763477-T-A is described in ClinVar as [Benign]. Clinvar id is 262229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC52A3	NM_033409.4	c.1073+21A>T		intron_variant		ENST00000645534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC52A3	ENST00000645534.1	c.1073+21A>T		intron_variant			NM_033409.4	P1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2764 AN: 152144 Hom.: 116 Cov.: 33

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00495

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.0244 AC: 6111 AN: 250746 Hom.: 330 AF XY: 0.0235 AC XY: 3184 AN XY: 135582

Gnomad AFR exome AF: 0.0194

Gnomad AMR exome AF: 0.00938

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.173

Gnomad SAS exome AF: 0.0241

Gnomad FIN exome AF: 0.0337

Gnomad NFE exome AF: 0.00590

Gnomad OTH exome AF: 0.0181

GnomAD4 exome AF: 0.0128 AC: 18668 AN: 1461434 Hom.: 1047 Cov.: 32 AF XY: 0.0133 AC XY: 9659 AN XY: 727010

Gnomad4 AFR exome AF: 0.0197

Gnomad4 AMR exome AF: 0.00933

Gnomad4 ASJ exome AF: 0.00601

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.0239

Gnomad4 FIN exome AF: 0.0319

Gnomad4 NFE exome AF: 0.00405

Gnomad4 OTH exome AF: 0.0154

GnomAD4 genome AF: 0.0181 AC: 2763 AN: 152262 Hom.: 114 Cov.: 33 AF XY: 0.0208 AC XY: 1546 AN XY: 74438

Gnomad4 AFR AF: 0.0196

Gnomad4 AMR AF: 0.0127

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.00494

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0114 Hom.: 4

Bravo AF: 0.0188

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	13
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73576869; hg19: chr20-744121; COSMIC: COSV54078282;