Variant 8-144359385-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001363118.2(SLC52A2):c.92G>C(p.Trp31Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLC52A2
NM_001363118.2 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

SLC52A2 (HGNC:30224): (solute carrier family 52 member 2) This gene encodes a membrane protein which belongs to the riboflavin transporter family. In humans, riboflavin must be obtained by intestinal absorption because it cannot be synthesized by the body. The water-soluble vitamin riboflavin is processed to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which then act as intermediaries in many cellular metabolic reactions. Paralogous members of the riboflavin transporter gene family are located on chromosomes 17 and 20. Unlike other members of this family, this gene has higher expression in brain tissue than small intestine. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. Mutations in this gene have been associated with Brown-Vialetto-Van Laere syndrome 2 - an autosomal recessive progressive neurologic disorder characterized by deafness, bulbar dysfunction, and axial and limb hypotonia. [provided by RefSeq, Jul 2012]

SLC52A2 links:

SLC52A2 (HGNC:):

SLC52A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.933

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC52A2	NM_001363118.2 linkuse as main transcript	c.92G>C	p.Trp31Ser	missense_variant	2/5	ENST00000643944.2	NP_001350047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC52A2	ENST00000643944.2 linkuse as main transcript	c.92G>C	p.Trp31Ser	missense_variant	2/5		NM_001363118.2	ENSP00000496184.2		Q9HAB3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

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

Bravo

AF:

0.00000378

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

Brown-Vialetto-van Laere syndrome 2

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

.;D;D;.;D;T;D;D;.;D

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.95

M_CAP

Pathogenic

0.80

MetaRNN

Pathogenic

0.93

D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.35

MutationAssessor

Pathogenic

3.4

.;M;M;.;M;.;M;M;.;M

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-13

D;D;D;D;D;D;D;D;D;.

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;.

Polyphen

1.0

.;D;D;.;D;.;D;D;.;D

Vest4

0.94, 0.94, 0.84

MutPred

0.68

Loss of catalytic residue at W31 (P = 0.0824);Loss of catalytic residue at W31 (P = 0.0824);Loss of catalytic residue at W31 (P = 0.0824);Loss of catalytic residue at W31 (P = 0.0824);Loss of catalytic residue at W31 (P = 0.0824);Loss of catalytic residue at W31 (P = 0.0824);Loss of catalytic residue at W31 (P = 0.0824);Loss of catalytic residue at W31 (P = 0.0824);Loss of catalytic residue at W31 (P = 0.0824);Loss of catalytic residue at W31 (P = 0.0824);

MVP

0.86

MPC

0.69

ClinPred

1.0

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.92

gMVP

0.87

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

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