rs3746802

Variant names:

• chr20-763664-T-C
• rs3746802
• NM_033409.4:c.907A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-763664-T-C
• chr20-763664-T-G

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.907A>G​(p.Ile303Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,614,092 control chromosomes in the GnomAD database, including 9,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I303L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.094 (711 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8997 hom.)
• Consequence: SLC52A3 NM_033409.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 7.92
• Publications: 22 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028273165).
• BP6: Variant 20-763664-T-C is Benign according to our data. Variant chr20-763664-T-C is described in ClinVar as Benign. ClinVar VariationId is 262241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 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.907A>G	p.Ile303Val	missense	Exon 3 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.907A>G	p.Ile303Val	missense	Exon 4 of 6	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.907A>G	p.Ile303Val	missense	Exon 4 of 6	NP_001357015.1	Q9NQ40-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	ENST00000645534.1	MANE Select	c.907A>G	p.Ile303Val	missense	Exon 3 of 5	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000217254.11	TSL:5	c.907A>G	p.Ile303Val	missense	Exon 4 of 6	ENSP00000217254.7	Q9NQ40-1
	SLC52A3	ENST00000488495.3	TSL:3	c.907A>G	p.Ile303Val	missense	Exon 3 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 14294 AN: 152106 Hom.: 709 Cov.: 33

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0880

GnomAD2 exomes AF: 0.103 AC: 25862 AN: 251384 AF XY: 0.107

Gnomad AFR exome AF: 0.0724

Gnomad AMR exome AF: 0.0606

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.0912

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.109 AC: 158688 AN: 1461868 Hom.: 8997 Cov.: 35 AF XY: 0.109 AC XY: 79544 AN XY: 727234

African (AFR) AF: 0.0663 AC: 2219 AN: 33480

American (AMR) AF: 0.0628 AC: 2810 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 3349 AN: 26136

East Asian (EAS) AF: 0.100 AC: 3979 AN: 39700

South Asian (SAS) AF: 0.140 AC: 12116 AN: 86258

European-Finnish (FIN) AF: 0.112 AC: 6006 AN: 53406

Middle Eastern (MID) AF: 0.0803 AC: 463 AN: 5768

European-Non Finnish (NFE) AF: 0.109 AC: 121326 AN: 1112000

Other (OTH) AF: 0.106 AC: 6420 AN: 60396

GnomAD4 genome AF: 0.0940 AC: 14306 AN: 152224 Hom.: 711 Cov.: 33 AF XY: 0.0938 AC XY: 6982 AN XY: 74416

African (AFR) AF: 0.0734 AC: 3049 AN: 41558

American (AMR) AF: 0.0696 AC: 1065 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3472

East Asian (EAS) AF: 0.103 AC: 533 AN: 5160

South Asian (SAS) AF: 0.135 AC: 653 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1155 AN: 10606

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7200 AN: 67988

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.103 Hom.: 3805

Bravo AF: 0.0886

TwinsUK AF: 0.110 AC: 408

ALSPAC AF: 0.114 AC: 441

ESP6500AA AF: 0.0788 AC: 347

ESP6500EA AF: 0.110 AC: 943

ExAC AF: 0.105 AC: 12782

Asia WGS AF: 0.151 AC: 525 AN: 3478

EpiCase AF: 0.100

EpiControl AF: 0.0954

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Brown-Vialetto-van Laere syndrome 1 (1)
-	-	1	Progressive bulbar palsy of childhood;C0796274:Brown-Vialetto-van Laere syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0082	T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.85	N
REVEL	Uncertain	0.40
Sift	Benign	0.089	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.23
MPC		0.71
ClinPred		0.072	T
GERP RS		5.0
Varity_R		0.17
gMVP		0.31
Mutation Taster		=96/4	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: rs3746802; hg19: chr20-744308; COSMIC: COSV54076870;