chr20-763183-G-A

Variant names:

• chr20-763183-G-A
• rs910858
• NM_033409.4:c.1073+315C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033409.4(SLC52A3):​c.1073+315C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,092 control chromosomes in the GnomAD database, including 33,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (33535 hom., cov: 34)
• Consequence: SLC52A3 NM_033409.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.478
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 20-763183-G-A is Benign according to our data. Variant chr20-763183-G-A is described in ClinVar as Benign. ClinVar VariationId is 1252697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 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.1073+315C>T		intron	N/A	NP_212134.3
	SLC52A3	NM_001370085.1		c.1073+315C>T		intron	N/A	NP_001357014.1
	SLC52A3	NM_001370086.1		c.1073+315C>T		intron	N/A	NP_001357015.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A3	ENST00000645534.1	MANE Select	c.1073+315C>T		intron	N/A	ENSP00000494193.1
	SLC52A3	ENST00000675066.1		c.*293C>T		3_prime_UTR	Exon 3 of 3	ENSP00000501902.1
	SLC52A3	ENST00000217254.11	TSL:5	c.1073+315C>T		intron	N/A	ENSP00000217254.7

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98512 AN: 151974 Hom.: 33504 Cov.: 34

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.648 AC: 98588 AN: 152092 Hom.: 33535 Cov.: 34 AF XY: 0.651 AC XY: 48365 AN XY: 74326

African (AFR) AF: 0.424 AC: 17578 AN: 41486

American (AMR) AF: 0.645 AC: 9849 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2550 AN: 3466

East Asian (EAS) AF: 0.869 AC: 4477 AN: 5154

South Asian (SAS) AF: 0.735 AC: 3544 AN: 4824

European-Finnish (FIN) AF: 0.763 AC: 8064 AN: 10562

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50208 AN: 68010

Other (OTH) AF: 0.667 AC: 1408 AN: 2110

Alfa AF: 0.710 Hom.: 63510

Bravo AF: 0.634

Asia WGS AF: 0.762 AC: 2653 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.85
DANN	Benign	0.75
PhyloP100		-0.48
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: rs910858; hg19: chr20-743827;