rs13042395

Variant names:

• chr20-773867-C-T
• rs13042395
• NM_001370085.1:c.-238+2088G>A

Variant summary

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

The NM_001370085.1(SLC52A3):​c.-238+2088G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 152,292 control chromosomes in the GnomAD database, including 705 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 0.063 (705 hom., cov: 32)
• Consequence: SLC52A3 NM_001370085.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 36 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_001370085.1	c.-238+2088G>A		intron_variant	Intron 1 of 5		NP_001357014.1
SLC52A3	NM_001370086.1	c.-747+2088G>A		intron_variant	Intron 1 of 5		NP_001357015.1
SLC52A3	XM_024451821.1	c.-238+1024G>A		intron_variant	Intron 1 of 5		XP_024307589.1
SLC52A3	XM_047439868.1	c.-237-5385G>A		intron_variant	Intron 1 of 5		XP_047295824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000217254.11	c.-238+2088G>A		intron_variant	Intron 1 of 5	5		ENSP00000217254.7
SLC52A3	ENST00000676154.1	c.-52+2088G>A		intron_variant	Intron 1 of 2			ENSP00000501807.1
SLC52A3	ENST00000674666.1	c.-747+2088G>A		intron_variant	Intron 1 of 2			ENSP00000502783.1
SLC52A3	ENST00000675466.1	n.29+2088G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9571 AN: 152174 Hom.: 708 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.0312

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0718

Gnomad OTH AF: 0.0698

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

GnomAD4 genome AF: 0.0628 AC: 9557 AN: 152292 Hom.: 705 Cov.: 32 AF XY: 0.0623 AC XY: 4637 AN XY: 74468

African (AFR) AF: 0.0154 AC: 642 AN: 41570

American (AMR) AF: 0.0476 AC: 729 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2156 AN: 5152

South Asian (SAS) AF: 0.0306 AC: 148 AN: 4832

European-Finnish (FIN) AF: 0.0440 AC: 467 AN: 10620

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0718 AC: 4882 AN: 68018

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

Alfa AF: 0.0661 Hom.: 216

Bravo AF: 0.0640

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		-0.24

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: rs13042395; hg19: chr20-754511;