chr20-762576-T-C

Variant names:

• chr20-762576-T-C
• rs2317024
• NM_033409.4:c.1074-752A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033409.4(SLC52A3):​c.1074-752A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,072 control chromosomes in the GnomAD database, including 10,448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10448 hom., cov: 33)
• Consequence: SLC52A3 NM_033409.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 2 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: ClinGen, Ambry Genetics, PanelApp Australia, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• progressive bulbar palsy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	NM_033409.4	MANE Select	c.1074-752A>G		intron	N/A	NP_212134.3
	SLC52A3	NM_001370085.1		c.1074-752A>G		intron	N/A	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.1074-752A>G		intron	N/A	NP_001357015.1	Q9NQ40-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	ENST00000645534.1	MANE Select	c.1074-752A>G		intron	N/A	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000675066.1		c.*900A>G		3_prime_UTR	Exon 3 of 3	ENSP00000501902.1	A0A6Q8PFQ2
	SLC52A3	ENST00000217254.11	TSL:5	c.1074-752A>G		intron	N/A	ENSP00000217254.7	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54291 AN: 151954 Hom.: 10440 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.361

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.357 AC: 54321 AN: 152072 Hom.: 10448 Cov.: 33 AF XY: 0.364 AC XY: 27067 AN XY: 74342

African (AFR) AF: 0.227 AC: 9417 AN: 41486

American (AMR) AF: 0.404 AC: 6173 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1307 AN: 3468

East Asian (EAS) AF: 0.661 AC: 3415 AN: 5170

South Asian (SAS) AF: 0.436 AC: 2101 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4682 AN: 10576

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26036 AN: 67944

Other (OTH) AF: 0.359 AC: 758 AN: 2110

Alfa AF: 0.371 Hom.: 22808

Bravo AF: 0.353

Asia WGS AF: 0.511 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.67
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2317024; hg19: chr20-743220;