20-760742-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_033409.4(SLC52A3):c.*284G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 510,020 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (16 hom.)
• Consequence: SLC52A3 NM_033409.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0370

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-760742-C-T is Benign according to our data. Variant chr20-760742-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1204306.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00532 (811/152310) while in subpopulation NFE AF= 0.00747 (508/68036). AF 95% confidence interval is 0.00693. There are 5 homozygotes in gnomad4. There are 405 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC52A3	NM_033409.4	c.*284G>A		3_prime_UTR_variant	5/5	ENST00000645534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC52A3	ENST00000645534.1	c.*284G>A		3_prime_UTR_variant	5/5		NM_033409.4	P1

Frequencies

GnomAD3 genomes AF: 0.00533 AC: 811 AN: 152192 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00747

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00597 AC: 2136 AN: 357710 Hom.: 16 Cov.: 0 AF XY: 0.00561 AC XY: 1038 AN XY: 185088

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.000661

Gnomad4 ASJ exome AF: 0.0102

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000133

Gnomad4 FIN exome AF: 0.0143

Gnomad4 NFE exome AF: 0.00703

Gnomad4 OTH exome AF: 0.00585

GnomAD4 genome AF: 0.00532 AC: 811 AN: 152310 Hom.: 5 Cov.: 32 AF XY: 0.00544 AC XY: 405 AN XY: 74462

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.00747

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00225 Hom.: 0

Bravo AF: 0.00403

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.8
Dann	Benign	0.43

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: rs73069709; hg19: chr20-741386;