17-5033075-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017986.4(SLC52A1):c.1229C>A(p.Ala410Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000868 in 1,613,622 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

SLC52A1
NM_017986.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031155378).

BS2

High AC in GnomAd at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC52A1	NM_017986.4 linkuse as main transcript	c.1229C>A	p.Ala410Glu	missense_variant	5/5	ENST00000254853.10
LOC105371501	XR_002958101.2 linkuse as main transcript	n.339+1406G>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.1229C>A	p.Ala410Glu	missense_variant	5/5	1	NM_017986.4	P1	Q9NWF4-1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

250422

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00148

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:

0.0000177

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461330

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00

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:

0.00000809

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000479

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000886

Hom.:

Bravo

AF:

0.000518

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ariboflavinosis

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 08, 2022

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 841357). This variant has not been reported in the literature in individuals affected with SLC52A1-related conditions. This variant is present in population databases (rs112874988, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 410 of the SLC52A1 protein (p.Ala410Glu). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.17

Cadd

Benign

Dann

Benign

0.93

DEOGEN2

Benign

0.036

T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.31

M_CAP

Benign

0.013

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

0.58

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.48

N;N

REVEL

Uncertain

0.38

Sift

Uncertain

0.023

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.88

P;P

Vest4

0.47

MVP

0.53

MPC

0.37

ClinPred

0.087

GERP RS

-0.10

Varity_R

0.20

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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