rs73576869

Variant names:

• chr20-763477-T-A
• rs73576869
• NM_033409.4:c.1073+21A>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.0890
• Publications: 4 publications found

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]

SLC52A3 Gene-Disease associations (from GenCC):

• Brown-Vialetto-van Laere syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• progressive bulbar palsy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033409.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	NM_033409.4	MANE Select	c.1073+21A>T		intron	N/A	NP_212134.3
	SLC52A3	NM_001370085.1		c.1073+21A>T		intron	N/A	NP_001357014.1
	SLC52A3	NM_001370086.1		c.1073+21A>T		intron	N/A	NP_001357015.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	ENST00000645534.1	MANE Select	c.1073+21A>T		intron	N/A	ENSP00000494193.1
	SLC52A3	ENST00000675066.1		c.1094A>T	p.Ter365Leuext*?	stop_lost	Exon 3 of 3	ENSP00000501902.1
	SLC52A3	ENST00000217254.11	TSL:5	c.1073+21A>T		intron	N/A	ENSP00000217254.7

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

GnomAD2 exomes AF: 0.0244 AC: 6111 AN: 250746 AF XY: 0.0235

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 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

African (AFR) AF: 0.0197 AC: 658 AN: 33472

American (AMR) AF: 0.00933 AC: 417 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00601 AC: 157 AN: 26132

East Asian (EAS) AF: 0.207 AC: 8212 AN: 39698

South Asian (SAS) AF: 0.0239 AC: 2064 AN: 86236

European-Finnish (FIN) AF: 0.0319 AC: 1695 AN: 53194

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5762

European-Non Finnish (NFE) AF: 0.00405 AC: 4507 AN: 1111854

Other (OTH) AF: 0.0154 AC: 929 AN: 60374

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

African (AFR) AF: 0.0196 AC: 814 AN: 41546

American (AMR) AF: 0.0127 AC: 195 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.178 AC: 919 AN: 5166

South Asian (SAS) AF: 0.0220 AC: 106 AN: 4828

European-Finnish (FIN) AF: 0.0317 AC: 336 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00494 AC: 336 AN: 68014

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0114 Hom.: 4

Bravo AF: 0.0188

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		0.089
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73576869; hg19: chr20-744121; COSMIC: COSV54078282;