NM_033409.4:c.645C>T

Variant names:

• chr20-763926-G-A
• rs6054605
• NM_033409.4:c.645C>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.645C>T​(p.Pro215Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,613,664 control chromosomes in the GnomAD database, including 6,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (734 hom., cov: 32)
  • Exomes 𝑓: 0.064 (5777 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.72
• Publications: 10 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 20-763926-G-A is Benign according to our data. Variant chr20-763926-G-A is described in ClinVar as Benign. ClinVar VariationId is 262237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 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.645C>T	p.Pro215Pro	synonymous	Exon 3 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.645C>T	p.Pro215Pro	synonymous	Exon 4 of 6	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.645C>T	p.Pro215Pro	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.645C>T	p.Pro215Pro	synonymous	Exon 3 of 5	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000217254.11	TSL:5	c.645C>T	p.Pro215Pro	synonymous	Exon 4 of 6	ENSP00000217254.7	Q9NQ40-1
	SLC52A3	ENST00000488495.3	TSL:3	c.645C>T	p.Pro215Pro	synonymous	Exon 3 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10181 AN: 152024 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.0834

GnomAD2 exomes AF: 0.0854 AC: 21331 AN: 249854 AF XY: 0.0829

Gnomad AFR exome AF: 0.0496

Gnomad AMR exome AF: 0.0600

Gnomad ASJ exome AF: 0.0669

Gnomad EAS exome AF: 0.467

Gnomad FIN exome AF: 0.0271

Gnomad NFE exome AF: 0.0577

Gnomad OTH exome AF: 0.0803

GnomAD4 exome AF: 0.0637 AC: 93128 AN: 1461522 Hom.: 5777 Cov.: 64 AF XY: 0.0635 AC XY: 46187 AN XY: 727016

African (AFR) AF: 0.0465 AC: 1558 AN: 33476

American (AMR) AF: 0.0592 AC: 2645 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 1730 AN: 26130

East Asian (EAS) AF: 0.393 AC: 15601 AN: 39676

South Asian (SAS) AF: 0.0548 AC: 4721 AN: 86220

European-Finnish (FIN) AF: 0.0285 AC: 1521 AN: 53392

Middle Eastern (MID) AF: 0.0914 AC: 527 AN: 5764

European-Non Finnish (NFE) AF: 0.0537 AC: 59701 AN: 1111832

Other (OTH) AF: 0.0849 AC: 5124 AN: 60376

GnomAD4 genome AF: 0.0669 AC: 10183 AN: 152142 Hom.: 734 Cov.: 32 AF XY: 0.0689 AC XY: 5126 AN XY: 74380

African (AFR) AF: 0.0473 AC: 1965 AN: 41504

American (AMR) AF: 0.0748 AC: 1144 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2242 AN: 5138

South Asian (SAS) AF: 0.0718 AC: 347 AN: 4830

European-Finnish (FIN) AF: 0.0249 AC: 264 AN: 10610

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0544 AC: 3699 AN: 67992

Other (OTH) AF: 0.0830 AC: 175 AN: 2108

Alfa AF: 0.0631 Hom.: 2004

Bravo AF: 0.0729

Asia WGS AF: 0.195 AC: 675 AN: 3478

EpiCase AF: 0.0630

EpiControl AF: 0.0667

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.63
PhyloP100		-4.7
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: rs6054605; hg19: chr20-744570; COSMIC: COSV54077373;