20-761203-A-G

Variant names:

• chr20-761203-A-G
• rs910857
• NM_033409.4:c.1233T>C

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.1233T>C​(p.Ser411Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,558,282 control chromosomes in the GnomAD database, including 397,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35962 hom., cov: 35)
  • Exomes 𝑓: 0.72 (361991 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.24
• Publications: 23 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=-0.51).
• BP6: Variant 20-761203-A-G is Benign according to our data. Variant chr20-761203-A-G is described in ClinVar as Benign. ClinVar VariationId is 262230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 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.1233T>C	p.Ser411Ser	synonymous	Exon 5 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.1233T>C	p.Ser411Ser	synonymous	Exon 6 of 6	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.1233T>C	p.Ser411Ser	synonymous	Exon 6 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.1233T>C	p.Ser411Ser	synonymous	Exon 5 of 5	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000217254.11	TSL:5	c.1233T>C	p.Ser411Ser	synonymous	Exon 6 of 6	ENSP00000217254.7	Q9NQ40-1
	SLC52A3	ENST00000488495.3	TSL:3	c.1233T>C	p.Ser411Ser	synonymous	Exon 5 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104196 AN: 152114 Hom.: 35935 Cov.: 35

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.678

GnomAD2 exomes AF: 0.681 AC: 112365 AN: 165046 AF XY: 0.687

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.706

Gnomad EAS exome AF: 0.525

Gnomad FIN exome AF: 0.733

Gnomad NFE exome AF: 0.715

Gnomad OTH exome AF: 0.683

GnomAD4 exome AF: 0.716 AC: 1006058 AN: 1406048 Hom.: 361991 Cov.: 77 AF XY: 0.717 AC XY: 497785 AN XY: 694290

African (AFR) AF: 0.629 AC: 20085 AN: 31924

American (AMR) AF: 0.608 AC: 22518 AN: 37034

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 17754 AN: 25262

East Asian (EAS) AF: 0.473 AC: 17208 AN: 36408

South Asian (SAS) AF: 0.732 AC: 58585 AN: 80000

European-Finnish (FIN) AF: 0.737 AC: 35588 AN: 48310

Middle Eastern (MID) AF: 0.686 AC: 3237 AN: 4722

European-Non Finnish (NFE) AF: 0.729 AC: 789893 AN: 1084214

Other (OTH) AF: 0.708 AC: 41190 AN: 58174

GnomAD4 genome AF: 0.685 AC: 104278 AN: 152234 Hom.: 35962 Cov.: 35 AF XY: 0.685 AC XY: 50974 AN XY: 74444

African (AFR) AF: 0.636 AC: 26444 AN: 41558

American (AMR) AF: 0.622 AC: 9516 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2418 AN: 3470

East Asian (EAS) AF: 0.519 AC: 2675 AN: 5156

South Asian (SAS) AF: 0.739 AC: 3570 AN: 4830

European-Finnish (FIN) AF: 0.751 AC: 7967 AN: 10612

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49337 AN: 67990

Other (OTH) AF: 0.677 AC: 1430 AN: 2112

Alfa AF: 0.698 Hom.: 59234

Bravo AF: 0.673

Asia WGS AF: 0.609 AC: 2118 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Brown-Vialetto-van Laere syndrome 1 (2)
-	-	2	not provided (2)
-	-	1	Progressive bulbar palsy of childhood (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		1.2
Mutation Taster		=94/6	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: rs910857; hg19: chr20-741847; COSMIC: COSV54077188;