20-763738-G-T

Variant names:

• chr20-763738-G-T
• rs3746803
• NM_033409.4:c.833C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033409.4(SLC52A3):​c.833C>A​(p.Thr278Lys) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T278M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC52A3 NM_033409.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04516962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4	c.833C>A	p.Thr278Lys	missense_variant	Exon 3 of 5	ENST00000645534.1	NP_212134.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000645534.1	c.833C>A	p.Thr278Lys	missense_variant	Exon 3 of 5		NM_033409.4	ENSP00000494193.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.8
DANN	Benign	0.27
DEOGEN2	Benign	0.0060	T;T;.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.35	.;.;T;.;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.045	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.77	N;N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.95	.;.;N;N;.
REVEL	Benign	0.059
Sift	Benign	0.95	.;.;T;T;.
Sift4G	Benign	0.92	.;T;T;T;.
Polyphen		0.0020	B;B;B;B;B
Vest4		0.065, 0.080, 0.063
MutPred		0.28		Gain of ubiquitination at T278 (P = 0.0014);Gain of ubiquitination at T278 (P = 0.0014);Gain of ubiquitination at T278 (P = 0.0014);Gain of ubiquitination at T278 (P = 0.0014);Gain of ubiquitination at T278 (P = 0.0014);
MVP		0.23
MPC		0.37
ClinPred		0.038	T
GERP RS		2.4
Varity_R		0.032
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs3746803; hg19: chr20-744382;