chr20-761140-G-A

Variant names:

• chr20-761140-G-A
• rs758570021
• NM_033409.4:c.1296C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_033409.4(SLC52A3):​c.1296C>T​(p.Cys432Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,439,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• 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: 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=-0.237 with no splicing effect.

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.1296C>T	p.Cys432Cys	synonymous	Exon 5 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.1296C>T	p.Cys432Cys	synonymous	Exon 6 of 6	NP_001357014.1
	SLC52A3	NM_001370086.1		c.1296C>T	p.Cys432Cys	synonymous	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.1296C>T	p.Cys432Cys	synonymous	Exon 5 of 5	ENSP00000494193.1
	SLC52A3	ENST00000473664.2	TSL:5	c.790C>T	p.Arg264Trp	missense	Exon 3 of 3	ENSP00000502741.1
	SLC52A3	ENST00000217254.11	TSL:5	c.1296C>T	p.Cys432Cys	synonymous	Exon 6 of 6	ENSP00000217254.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000985 AC: 2 AN: 203072 AF XY: 0.0000180

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000684

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1439170 Hom.: 0 Cov.: 30 AF XY: 0.00000420 AC XY: 3 AN XY: 714030

African (AFR) AF: 0.00 AC: 0 AN: 32868

American (AMR) AF: 0.00 AC: 0 AN: 41836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25742

East Asian (EAS) AF: 0.0000262 AC: 1 AN: 38182

South Asian (SAS) AF: 0.0000362 AC: 3 AN: 82932

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5496

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102270

Other (OTH) AF: 0.00 AC: 0 AN: 59480

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.6
DANN	Benign	0.95
PhyloP100		-0.24
Mutation Taster		=100/0	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: rs758570021; hg19: chr20-741784; COSMIC: COSV54078579;