NM_033409.4:c.339C>T

Variant names:

• chr20-765436-G-A
• rs151229044
• NM_033409.4:c.339C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_033409.4(SLC52A3):​c.339C>T​(p.Phe113Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.00111 in 1,613,158 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00076 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 4.20
• Publications: 0 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: Ambry Genetics, G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• progressive bulbar palsy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 20-765436-G-A is Benign according to our data. Variant chr20-765436-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 543063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000762 (116/152324) while in subpopulation SAS AF = 0.00352 (17/4826). AF 95% confidence interval is 0.00224. There are 1 homozygotes in GnomAd4. There are 52 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.339C>T	p.Phe113Phe	synonymous	Exon 2 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.339C>T	p.Phe113Phe	synonymous	Exon 3 of 6	NP_001357014.1
	SLC52A3	NM_001370086.1		c.339C>T	p.Phe113Phe	synonymous	Exon 3 of 6	NP_001357015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	ENST00000645534.1	MANE Select	c.339C>T	p.Phe113Phe	synonymous	Exon 2 of 5	ENSP00000494193.1
	SLC52A3	ENST00000217254.11	TSL:5	c.339C>T	p.Phe113Phe	synonymous	Exon 3 of 6	ENSP00000217254.7
	SLC52A3	ENST00000488495.3	TSL:3	c.339C>T	p.Phe113Phe	synonymous	Exon 2 of 5	ENSP00000494009.1

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 116 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00105 AC: 260 AN: 247002 AF XY: 0.00130

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000644

Gnomad ASJ exome AF: 0.000501

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000949

Gnomad NFE exome AF: 0.00116

Gnomad OTH exome AF: 0.000994

GnomAD4 exome AF: 0.00115 AC: 1677 AN: 1460834 Hom.: 2 Cov.: 32 AF XY: 0.00119 AC XY: 865 AN XY: 726610

African (AFR) AF: 0.000209 AC: 7 AN: 33464

American (AMR) AF: 0.000809 AC: 36 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00309 AC: 266 AN: 86130

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53370

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.00111 AC: 1237 AN: 1111478

Other (OTH) AF: 0.00161 AC: 97 AN: 60350

GnomAD4 genome AF: 0.000762 AC: 116 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000698 AC XY: 52 AN XY: 74484

African (AFR) AF: 0.000120 AC: 5 AN: 41568

American (AMR) AF: 0.000392 AC: 6 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4826

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00121 AC: 82 AN: 68036

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00113 Hom.: 0

Bravo AF: 0.000805

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Brown-Vialetto-van Laere syndrome 1 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)
-	-	1	SLC52A3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		4.2
PromoterAI		-0.012	Neutral
Mutation Taster		=75/25	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: rs151229044; hg19: chr20-746080;