17-5033041-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017986.4(SLC52A1):c.1263T>A(p.Leu421=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,508 control chromosomes in the GnomAD database, including 16,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L421L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.14 ( 1563 hom., cov: 31)

Exomes 𝑓: 0.14 ( 14605 hom. )

Consequence

SLC52A1
NM_017986.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.12

Variant links:

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]

SLC52A1 links:

LOC105371501 (HGNC:):

LOC105371501 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-5033041-A-T is Benign according to our data. Variant chr17-5033041-A-T is described in ClinVar as [Benign]. Clinvar id is 1166171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC52A1	NM_017986.4 linkuse as main transcript	c.1263T>A	p.Leu421=	synonymous_variant	5/5	ENST00000254853.10
LOC105371501	XR_002958101.2 linkuse as main transcript	n.339+1372A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC52A1	ENST00000254853.10 linkuse as main transcript	c.1263T>A	p.Leu421=	synonymous_variant	5/5	1	NM_017986.4	P1	Q9NWF4-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21146

AN:

152010

Hom.:

1561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0599

Gnomad SAS

AF:

0.0455

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.126

AC:

31599

AN:

250180

Hom.:

2330

AF XY:

0.123

AC XY:

16664

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.143

Gnomad EAS exome

AF:

0.0574

Gnomad SAS exome

AF:

0.0445

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.137

AC:

200879

AN:

1461380

Hom.:

14605

Cov.:

AF XY:

0.135

AC XY:

97835

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.0791

Gnomad4 SAS exome

AF:

0.0464

Gnomad4 FIN exome

AF:

0.188

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.139

AC:

21167

AN:

152128

Hom.:

1563

Cov.:

AF XY:

0.139

AC XY:

10323

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.0601

Gnomad4 SAS

AF:

0.0456

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.145

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.104

Hom.:

240

Bravo

AF:

0.131

EpiCase

AF:

0.142

EpiControl

AF:

0.138

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SLC52A1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Ariboflavinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

1.1

Dann

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over