rs34376836

chr20-765535-G-Achr20-765535-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_033409.4(SLC52A3):c.240C>T(p.Gly80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,575,600 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (50 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (28 hom.)
• Consequence: SLC52A3 NM_033409.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.453

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-765535-G-A is Benign according to our data. Variant chr20-765535-G-A is described in ClinVar as [Benign]. Clinvar id is 262232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-765535-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.453 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1797/152224) while in subpopulation AFR AF= 0.0415 (1724/41524). AF 95% confidence interval is 0.0399. There are 50 homozygotes in gnomad4. There are 875 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC52A3	NM_033409.4	c.240C>T	p.Gly80=	synonymous_variant	2/5	ENST00000645534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC52A3	ENST00000645534.1	c.240C>T	p.Gly80=	synonymous_variant	2/5		NM_033409.4	P1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1781 AN: 152106 Hom.: 48 Cov.: 31

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00959

GnomAD3 exomes AF: 0.00307 AC: 572 AN: 186368 Hom.: 16 AF XY: 0.00227 AC XY: 225 AN XY: 99068

Gnomad AFR exome AF: 0.0451

Gnomad AMR exome AF: 0.00207

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000380

Gnomad OTH exome AF: 0.00101

GnomAD4 exome AF: 0.00118 AC: 1686 AN: 1423376 Hom.: 28 Cov.: 37 AF XY: 0.00105 AC XY: 740 AN XY: 704284

Gnomad4 AFR exome AF: 0.0434

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000490

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000192

Gnomad4 OTH exome AF: 0.00271

GnomAD4 genome AF: 0.0118 AC: 1797 AN: 152224 Hom.: 50 Cov.: 31 AF XY: 0.0118 AC XY: 875 AN XY: 74424

Gnomad4 AFR AF: 0.0415

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00949

Alfa AF: 0.00357 Hom.: 4

Bravo AF: 0.0134

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Gly80Gly in exon 2 of SLC52A3: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 5.50% (247/4494) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs34376836). -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2019	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Progressive bulbar palsy of childhood;C0796274:Brown-Vialetto-van Laere syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 12, 2021

- -

Brown-Vialetto-van Laere syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.52
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs34376836; hg19: chr20-746179;