rs139486822

Variant names:

• chr20-765766-G-A
• rs139486822
• NM_033409.4:c.9C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-765766-G-A
• chr20-765766-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_033409.4(SLC52A3):​c.9C>T​(p.Phe3Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,600,526 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (8 hom., cov: 31)
  • Exomes 𝑓: 0.010 (113 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.48
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 20-765766-G-A is Benign according to our data. Variant chr20-765766-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.48 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00791 (1106/139812) while in subpopulation AMR AF = 0.0129 (188/14574). AF 95% confidence interval is 0.0114. There are 8 homozygotes in GnomAd4. There are 517 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.9C>T	p.Phe3Phe	synonymous	Exon 2 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.9C>T	p.Phe3Phe	synonymous	Exon 3 of 6	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.9C>T	p.Phe3Phe	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.9C>T	p.Phe3Phe	synonymous	Exon 2 of 5	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000217254.11	TSL:5	c.9C>T	p.Phe3Phe	synonymous	Exon 3 of 6	ENSP00000217254.7	Q9NQ40-1
	SLC52A3	ENST00000488495.3	TSL:3	c.9C>T	p.Phe3Phe	synonymous	Exon 2 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.00791 AC: 1105 AN: 139692 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.000886

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.00653

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0150

GnomAD2 exomes AF: 0.00622 AC: 1491 AN: 239864 AF XY: 0.00595

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.00808

Gnomad ASJ exome AF: 0.000925

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00598

Gnomad NFE exome AF: 0.00935

Gnomad OTH exome AF: 0.00981

GnomAD4 exome AF: 0.0102 AC: 14939 AN: 1460714 Hom.: 113 Cov.: 36 AF XY: 0.00982 AC XY: 7136 AN XY: 726546

African (AFR) AF: 0.00164 AC: 55 AN: 33474

American (AMR) AF: 0.00936 AC: 418 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00169 AC: 44 AN: 26034

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39684

South Asian (SAS) AF: 0.000233 AC: 20 AN: 85946

European-Finnish (FIN) AF: 0.00738 AC: 392 AN: 53142

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5760

European-Non Finnish (NFE) AF: 0.0121 AC: 13477 AN: 1111696

Other (OTH) AF: 0.00840 AC: 507 AN: 60332

GnomAD4 genome AF: 0.00791 AC: 1106 AN: 139812 Hom.: 8 Cov.: 31 AF XY: 0.00755 AC XY: 517 AN XY: 68510

African (AFR) AF: 0.00228 AC: 83 AN: 36358

American (AMR) AF: 0.0129 AC: 188 AN: 14574

Ashkenazi Jewish (ASJ) AF: 0.000886 AC: 3 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4742

South Asian (SAS) AF: 0.000427 AC: 2 AN: 4682

European-Finnish (FIN) AF: 0.00653 AC: 64 AN: 9794

Middle Eastern (MID) AF: 0.0139 AC: 4 AN: 288

European-Non Finnish (NFE) AF: 0.0116 AC: 733 AN: 63202

Other (OTH) AF: 0.0149 AC: 29 AN: 1950

Alfa AF: 0.00872 Hom.: 20

Bravo AF: 0.00809

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Brown-Vialetto-van Laere syndrome 1 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)
-	-	1	Progressive bulbar palsy of childhood;C0796274:Brown-Vialetto-van Laere syndrome 1 (1)
-	-	1	SLC52A3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	9.0
DANN	Benign	0.79
PhyloP100		2.5
PromoterAI		-0.038	Neutral
Mutation Taster		=93/7	polymorphism

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: rs139486822; hg19: chr20-746410; COSMIC: COSV99448591;