rs3746807

Variant names:

• chr20-765319-G-A
• rs3746807
• NM_033409.4:c.456C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-765319-G-A
• chr20-765319-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033409.4(SLC52A3):​c.456C>T​(p.Pro152Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,613,980 control chromosomes in the GnomAD database, including 9,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (806 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8773 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.14
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 20-765319-G-A is Benign according to our data. Variant chr20-765319-G-A is described in ClinVar as Benign. ClinVar VariationId is 262234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 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.456C>T	p.Pro152Pro	synonymous	Exon 2 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.456C>T	p.Pro152Pro	synonymous	Exon 3 of 6	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.456C>T	p.Pro152Pro	synonymous	Exon 3 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.456C>T	p.Pro152Pro	synonymous	Exon 2 of 5	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000217254.11	TSL:5	c.456C>T	p.Pro152Pro	synonymous	Exon 3 of 6	ENSP00000217254.7	Q9NQ40-1
	SLC52A3	ENST00000488495.3	TSL:3	c.456C>T	p.Pro152Pro	synonymous	Exon 2 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15334 AN: 152016 Hom.: 805 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0917

GnomAD2 exomes AF: 0.0957 AC: 24062 AN: 251434 AF XY: 0.0941

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.0544

Gnomad ASJ exome AF: 0.0575

Gnomad EAS exome AF: 0.177

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.0908

GnomAD4 exome AF: 0.106 AC: 154446 AN: 1461846 Hom.: 8773 Cov.: 33 AF XY: 0.105 AC XY: 76092 AN XY: 727228

African (AFR) AF: 0.101 AC: 3365 AN: 33480

American (AMR) AF: 0.0566 AC: 2532 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 1468 AN: 26136

East Asian (EAS) AF: 0.217 AC: 8616 AN: 39700

South Asian (SAS) AF: 0.0652 AC: 5623 AN: 86258

European-Finnish (FIN) AF: 0.109 AC: 5821 AN: 53414

Middle Eastern (MID) AF: 0.0480 AC: 277 AN: 5768

European-Non Finnish (NFE) AF: 0.109 AC: 120737 AN: 1111970

Other (OTH) AF: 0.0995 AC: 6007 AN: 60396

GnomAD4 genome AF: 0.101 AC: 15363 AN: 152134 Hom.: 806 Cov.: 32 AF XY: 0.0998 AC XY: 7425 AN XY: 74368

African (AFR) AF: 0.105 AC: 4369 AN: 41494

American (AMR) AF: 0.0836 AC: 1277 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 175 AN: 3466

East Asian (EAS) AF: 0.180 AC: 926 AN: 5152

South Asian (SAS) AF: 0.0521 AC: 251 AN: 4818

European-Finnish (FIN) AF: 0.0983 AC: 1043 AN: 10614

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6992 AN: 67988

Other (OTH) AF: 0.0907 AC: 192 AN: 2116

Alfa AF: 0.102 Hom.: 3941

Bravo AF: 0.102

Asia WGS AF: 0.125 AC: 436 AN: 3478

EpiCase AF: 0.0961

EpiControl AF: 0.0962

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Brown-Vialetto-van Laere syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		-1.1
Mutation Taster		=99/1	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: rs3746807; hg19: chr20-745963; COSMIC: COSV54077450;