20-763971-G-A

Variant names:

• chr20-763971-G-A
• rs16992990
• NM_033409.4:c.600C>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.600C>T​(p.Pro200Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,598,728 control chromosomes in the GnomAD database, including 378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (332 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.68
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-763971-G-A is Benign according to our data. Variant chr20-763971-G-A is described in ClinVar as Benign. ClinVar VariationId is 262236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.065 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.600C>T	p.Pro200Pro	synonymous	Exon 3 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.600C>T	p.Pro200Pro	synonymous	Exon 4 of 6	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.600C>T	p.Pro200Pro	synonymous	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.600C>T	p.Pro200Pro	synonymous	Exon 3 of 5	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000217254.11	TSL:5	c.600C>T	p.Pro200Pro	synonymous	Exon 4 of 6	ENSP00000217254.7	Q9NQ40-1
	SLC52A3	ENST00000488495.3	TSL:3	c.600C>T	p.Pro200Pro	synonymous	Exon 3 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1576 AN: 151746 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00335

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.0432

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00202

Gnomad OTH AF: 0.0106

GnomAD2 exomes AF: 0.0174 AC: 3805 AN: 218302 AF XY: 0.0203

Gnomad AFR exome AF: 0.0172

Gnomad AMR exome AF: 0.00317

Gnomad ASJ exome AF: 0.0360

Gnomad EAS exome AF: 0.0437

Gnomad FIN exome AF: 0.000876

Gnomad NFE exome AF: 0.00306

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.00835 AC: 12079 AN: 1446864 Hom.: 332 Cov.: 61 AF XY: 0.0101 AC XY: 7283 AN XY: 718584

African (AFR) AF: 0.0183 AC: 607 AN: 33136

American (AMR) AF: 0.00300 AC: 124 AN: 41362

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 914 AN: 25844

East Asian (EAS) AF: 0.0344 AC: 1340 AN: 38920

South Asian (SAS) AF: 0.0683 AC: 5771 AN: 84474

European-Finnish (FIN) AF: 0.000950 AC: 50 AN: 52646

Middle Eastern (MID) AF: 0.0223 AC: 127 AN: 5694

European-Non Finnish (NFE) AF: 0.00207 AC: 2287 AN: 1104906

Other (OTH) AF: 0.0143 AC: 859 AN: 59882

GnomAD4 genome AF: 0.0104 AC: 1583 AN: 151864 Hom.: 46 Cov.: 32 AF XY: 0.0118 AC XY: 879 AN XY: 74200

African (AFR) AF: 0.0160 AC: 662 AN: 41394

American (AMR) AF: 0.00335 AC: 51 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3468

East Asian (EAS) AF: 0.0425 AC: 218 AN: 5130

South Asian (SAS) AF: 0.0712 AC: 341 AN: 4788

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10588

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00202 AC: 137 AN: 67938

Other (OTH) AF: 0.0123 AC: 26 AN: 2106

Alfa AF: 0.00510 Hom.: 7

Bravo AF: 0.00998

Asia WGS AF: 0.0570 AC: 197 AN: 3478

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
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.35
PhyloP100		-2.7
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: rs16992990; hg19: chr20-744615; COSMIC: COSV105094371;