Variant 1-234316611-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173508.4(SLC35F3):c.838G>A(p.Ala280Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,455,506 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SLC35F3
NM_173508.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.99

Variant links:

Genes affected

SLC35F3 (HGNC:23616): (solute carrier family 35 member F3) Involved in thiamine transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC35F3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35F3	NM_173508.4 link	c.838G>A	p.Ala280Thr	missense_variant	5/8	ENST00000366618.8	NP_775779.1	Q8IY50-2
SLC35F3	NM_001300845.2 link	c.631G>A	p.Ala211Thr	missense_variant	4/7		NP_001287774.1	Q8IY50-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35F3	ENST00000366618.8 link	c.838G>A	p.Ala280Thr	missense_variant	5/8	2	NM_173508.4	ENSP00000355577.3		Q8IY50-2
SLC35F3	ENST00000366617.3 link	c.631G>A	p.Ala211Thr	missense_variant	4/7	1		ENSP00000355576.3		Q8IY50-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250776

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1455506

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

722706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

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:

0.0000154

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000628

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.838G>A (p.A280T) alteration is located in exon 5 (coding exon 5) of the SLC35F3 gene. This alteration results from a G to A substitution at nucleotide position 838, causing the alanine (A) at amino acid position 280 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.067

.;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.0077

MetaRNN

Uncertain

0.69

D;D

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.4

.;L

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.29

Sift

Benign

0.13

T;T

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

D;D

Vest4

0.85

MutPred

0.51

.;Loss of helix (P = 0.0626);

MVP

0.093

MPC

1.6

ClinPred

0.75

GERP RS

5.7

Varity_R

0.19

gMVP

0.78

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