Genetic Variant NM_033409.4:c.1255G>T (chr20-761181-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033409.4(SLC52A3):c.1255G>T(p.Val419Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V419V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC52A3
NM_033409.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

0 publications found

Variant links:

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]

SLC52A3 Gene-Disease associations (from GenCC):

Brown-Vialetto-van Laere syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
progressive bulbar palsy
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

SLC52A3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18545964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033409.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC52A3	NM_033409.4	MANE Select	c.1255G>T	p.Val419Leu	missense	Exon 5 of 5	NP_212134.3
SLC52A3	NM_001370085.1		c.1255G>T	p.Val419Leu	missense	Exon 6 of 6	NP_001357014.1
SLC52A3	NM_001370086.1		c.1255G>T	p.Val419Leu	missense	Exon 6 of 6	NP_001357015.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC52A3	ENST00000645534.1	MANE Select	c.1255G>T	p.Val419Leu	missense	Exon 5 of 5	ENSP00000494193.1
SLC52A3	ENST00000217254.11	TSL:5	c.1255G>T	p.Val419Leu	missense	Exon 6 of 6	ENSP00000217254.7
SLC52A3	ENST00000488495.3	TSL:3	c.1255G>T	p.Val419Leu	missense	Exon 5 of 5	ENSP00000494009.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1418280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701640

African (AFR)

AF:

0.00

AC:

AN:

32324

American (AMR)

AF:

0.00

AC:

AN:

38512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25406

East Asian (EAS)

AF:

0.00

AC:

AN:

37014

South Asian (SAS)

AF:

0.00

AC:

AN:

80816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5060

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091488

Other (OTH)

AF:

0.00

AC:

AN:

58652

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0083

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.77

M_CAP

Benign

0.030

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

PhyloP100

1.2

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

REVEL

Benign

0.070

Sift

Benign

0.17

Sift4G

Benign

0.26

Polyphen

0.14

Vest4

0.17

MutPred

0.32

Loss of sheet (P = 0.0483)

MVP

0.63

MPC

0.31

ClinPred

0.71

GERP RS

3.1

Varity_R

0.16

gMVP

0.62

Mutation Taster

=61/39

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over