rs6140113

Variant names:

• chr20-763126-C-T
• rs6140113
• NM_033409.4:c.1073+372G>A

Variant summary

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

The NM_033409.4(SLC52A3):​c.1073+372G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,184 control chromosomes in the GnomAD database, including 2,637 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 0.17 (2637 hom., cov: 33)
• Consequence: SLC52A3 NM_033409.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 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+372G>A		intron	N/A	NP_212134.3
	SLC52A3	NM_001370085.1		c.1073+372G>A		intron	N/A	NP_001357014.1
	SLC52A3	NM_001370086.1		c.1073+372G>A		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+372G>A		intron	N/A	ENSP00000494193.1
	SLC52A3	ENST00000675066.1		c.*350G>A		3_prime_UTR	Exon 3 of 3	ENSP00000501902.1
	SLC52A3	ENST00000217254.11	TSL:5	c.1073+372G>A		intron	N/A	ENSP00000217254.7

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26212 AN: 152066 Hom.: 2631 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0991

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.172 AC: 26243 AN: 152184 Hom.: 2637 Cov.: 33 AF XY: 0.174 AC XY: 12950 AN XY: 74398

African (AFR) AF: 0.164 AC: 6828 AN: 41520

American (AMR) AF: 0.147 AC: 2245 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2674 AN: 5158

South Asian (SAS) AF: 0.205 AC: 988 AN: 4818

European-Finnish (FIN) AF: 0.134 AC: 1419 AN: 10594

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10905 AN: 68018

Other (OTH) AF: 0.180 AC: 379 AN: 2110

Alfa AF: 0.167 Hom.: 3718

Bravo AF: 0.175

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.59
DANN	Benign	0.68
PhyloP100		-1.4
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: rs6140113; hg19: chr20-743770;