17-5033011-GC-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_017986.4(SLC52A1):c.1292del(p.Ser431ThrfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SLC52A1 NM_017986.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.616

Genes affected

SLC52A1 (HGNC:30225): (solute carrier family 52 member 1) Biological redox reactions require electron donors and acceptor. Vitamin B2 is the source for the flavin in flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) which are common redox reagents. This gene encodes a member of the riboflavin (vitamin B2) transporter family. Haploinsufficiency of this protein can cause maternal riboflavin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2013]

LOC105371501 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC52A1	NM_017986.4	c.1292del	p.Ser431ThrfsTer13	frameshift_variant	5/5	ENST00000254853.10
LOC105371501	XR_002958101.2	n.339+1343del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC52A1	ENST00000254853.10	c.1292del	p.Ser431ThrfsTer13	frameshift_variant	5/5	1	NM_017986.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000799 AC: 2 AN: 250216 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135214

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000885

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461516 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ariboflavinosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

May 22, 2023

This variant has not been reported in the literature in individuals affected with SLC52A1-related conditions. This variant is present in population databases (rs754376857, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Ser431Thrfs*13) in the SLC52A1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acid(s) of the SLC52A1 protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

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: rs754376857; hg19: chr17-4936306;