chr20-765779-GTATCTGCCC-G

Variant names:

• chr20-765779-GTATCTGCCC-G
• rs11467076
• NM_033409.4:c.-14_-6delGGGCAGATA

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.-14_-6delGGGCAGATA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,608,422 control chromosomes in the GnomAD database, including 58,254 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (5977 hom., cov: 18)
  • Exomes 𝑓: 0.26 (52277 hom.)
• Consequence: SLC52A3 NM_033409.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.13
• Publications: 6 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 -16 ACMG points.

• BP6: Variant 20-765779-GTATCTGCCC-G is Benign according to our data. Variant chr20-765779-GTATCTGCCC-G is described in ClinVar as Benign. ClinVar VariationId is 262228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	NM_033409.4	MANE Select	c.-14_-6delGGGCAGATA		5_prime_UTR	Exon 2 of 5	NP_212134.3
	SLC52A3	NM_001370085.1		c.-14_-6delGGGCAGATA		5_prime_UTR	Exon 3 of 6	NP_001357014.1	Q9NQ40-1
	SLC52A3	NM_001370086.1		c.-14_-6delGGGCAGATA		5_prime_UTR	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.-14_-6delGGGCAGATA		5_prime_UTR	Exon 2 of 5	ENSP00000494193.1	Q9NQ40-1
	SLC52A3	ENST00000217254.11	TSL:5	c.-14_-6delGGGCAGATA		5_prime_UTR	Exon 3 of 6	ENSP00000217254.7	Q9NQ40-1
	SLC52A3	ENST00000488495.3	TSL:3	c.-14_-6delGGGCAGATA		5_prime_UTR	Exon 2 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41865 AN: 151712 Hom.: 5976 Cov.: 18

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.254

GnomAD2 exomes AF: 0.221 AC: 51450 AN: 232958 AF XY: 0.217

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.228

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.263 AC: 383449 AN: 1456592 Hom.: 52277 AF XY: 0.259 AC XY: 187604 AN XY: 724162

African (AFR) AF: 0.340 AC: 11346 AN: 33402

American (AMR) AF: 0.147 AC: 6525 AN: 44366

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4386 AN: 25796

East Asian (EAS) AF: 0.312 AC: 12353 AN: 39632

South Asian (SAS) AF: 0.116 AC: 9902 AN: 85298

European-Finnish (FIN) AF: 0.273 AC: 14376 AN: 52718

Middle Eastern (MID) AF: 0.181 AC: 1039 AN: 5740

European-Non Finnish (NFE) AF: 0.278 AC: 308164 AN: 1109458

Other (OTH) AF: 0.255 AC: 15358 AN: 60182

GnomAD4 genome AF: 0.276 AC: 41901 AN: 151830 Hom.: 5977 Cov.: 18 AF XY: 0.270 AC XY: 20061 AN XY: 74216

African (AFR) AF: 0.340 AC: 14081 AN: 41412

American (AMR) AF: 0.210 AC: 3206 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1262 AN: 5128

South Asian (SAS) AF: 0.109 AC: 525 AN: 4816

European-Finnish (FIN) AF: 0.270 AC: 2850 AN: 10568

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18592 AN: 67856

Other (OTH) AF: 0.254 AC: 534 AN: 2106

Alfa AF: 0.266 Hom.: 978

Bravo AF: 0.278

Asia WGS AF: 0.201 AC: 700 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Brown-Vialetto-van Laere syndrome 1 (1)
-	-	1	not provided (1)
-	-	1	Progressive bulbar palsy of childhood (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11467076; hg19: chr20-746423; COSMIC: COSV54076654;