20-761009-CGG-C

Variant names:

• chr20-761009-CGG-C
• rs3215628
• NM_033409.4:c.*15_*16delCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033409.4(SLC52A3):​c.*15_*16delCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLC52A3 NM_033409.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 5 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	NM_033409.4	MANE Select	c.*15_*16delCC		3_prime_UTR	Exon 5 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.*15_*16delCC		3_prime_UTR	Exon 6 of 6	NP_001357014.1
	SLC52A3	NM_001370086.1		c.*15_*16delCC		3_prime_UTR	Exon 6 of 6	NP_001357015.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	ENST00000645534.1	MANE Select	c.*15_*16delCC		3_prime_UTR	Exon 5 of 5	ENSP00000494193.1
	SLC52A3	ENST00000473664.2	TSL:5	c.919_920delCC	p.Pro307AlafsTer29	frameshift	Exon 3 of 3	ENSP00000502741.1
	SLC52A3	ENST00000217254.11	TSL:5	c.*15_*16delCC		3_prime_UTR	Exon 6 of 6	ENSP00000217254.7

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14

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: rs3215628; hg19: chr20-741653;