20-761009-CG-C

Variant names:

• chr20-761009-CG-C
• rs3215628
• NM_033409.4:c.*16delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_033409.4(SLC52A3):​c.*16delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,586,672 control chromosomes in the GnomAD database, including 14,079 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1343 hom., cov: 30)
  • Exomes 𝑓: 0.12 (12736 hom.)
• Consequence: SLC52A3 NM_033409.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.180
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 20-761009-CG-C is Benign according to our data. Variant chr20-761009-CG-C is described in ClinVar as Benign. ClinVar VariationId is 262227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	NM_033409.4	MANE Select	c.*16delC		3_prime_UTR	Exon 5 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.*16delC		3_prime_UTR	Exon 6 of 6	NP_001357014.1
	SLC52A3	NM_001370086.1		c.*16delC		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.*16delC		3_prime_UTR	Exon 5 of 5	ENSP00000494193.1
	SLC52A3	ENST00000473664.2	TSL:5	c.920delC	p.Pro307ArgfsTer28	frameshift	Exon 3 of 3	ENSP00000502741.1
	SLC52A3	ENST00000217254.11	TSL:5	c.*16delC		3_prime_UTR	Exon 6 of 6	ENSP00000217254.7

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17672 AN: 152070 Hom.: 1337 Cov.: 30

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.149 AC: 29852 AN: 199770 AF XY: 0.146

Gnomad AFR exome AF: 0.0664

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.349

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.120 AC: 171486 AN: 1434484 Hom.: 12736 Cov.: 28 AF XY: 0.121 AC XY: 85786 AN XY: 711584

African (AFR) AF: 0.0657 AC: 2143 AN: 32596

American (AMR) AF: 0.204 AC: 8379 AN: 41094

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3385 AN: 25704

East Asian (EAS) AF: 0.421 AC: 15789 AN: 37530

South Asian (SAS) AF: 0.163 AC: 13404 AN: 82390

European-Finnish (FIN) AF: 0.131 AC: 6579 AN: 50118

Middle Eastern (MID) AF: 0.126 AC: 696 AN: 5512

European-Non Finnish (NFE) AF: 0.104 AC: 113884 AN: 1100192

Other (OTH) AF: 0.122 AC: 7227 AN: 59348

GnomAD4 genome AF: 0.116 AC: 17693 AN: 152188 Hom.: 1343 Cov.: 30 AF XY: 0.122 AC XY: 9063 AN XY: 74406

African (AFR) AF: 0.0670 AC: 2783 AN: 41536

American (AMR) AF: 0.179 AC: 2738 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3472

East Asian (EAS) AF: 0.368 AC: 1897 AN: 5154

South Asian (SAS) AF: 0.168 AC: 809 AN: 4820

European-Finnish (FIN) AF: 0.129 AC: 1372 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7240 AN: 67994

Other (OTH) AF: 0.125 AC: 264 AN: 2110

Alfa AF: 0.113 Hom.: 190

Bravo AF: 0.117

Asia WGS AF: 0.255 AC: 883 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18
Mutation Taster		=100/0	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: rs3215628; hg19: chr20-741653; COSMIC: COSV54077207; COSMIC: COSV54077207;