Variant chr12-46188985-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030674.4(SLC38A1):c.1449T>A(p.Ser483Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLC38A1
NM_030674.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15

Variant links:

Genes affected

SLC38A1 (HGNC:13447): (solute carrier family 38 member 1) Amino acid transporters play essential roles in the uptake of nutrients, production of energy, chemical metabolism, detoxification, and neurotransmitter cycling. SLC38A1 is an important transporter of glutamine, an intermediate in the detoxification of ammonia and the production of urea. Glutamine serves as a precursor for the synaptic transmitter, glutamate (Gu et al., 2001 [PubMed 11325958]).[supplied by OMIM, Mar 2008]

SLC38A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.032924205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A1	NM_030674.4 linkuse as main transcript	c.1449T>A	p.Ser483Arg	missense_variant	17/17	ENST00000398637.10	NP_109599.3	Q9H2H9A0A024R124

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC38A1	ENST00000398637.10 linkuse as main transcript	c.1449T>A	p.Ser483Arg	missense_variant	17/17	1	NM_030674.4	ENSP00000381634.4	Q9H2H9
SLC38A1	ENST00000439706.5 linkuse as main transcript	c.1449T>A	p.Ser483Arg	missense_variant	18/18	1		ENSP00000398142.1	Q9H2H9
SLC38A1	ENST00000546893.5 linkuse as main transcript	c.1449T>A	p.Ser483Arg	missense_variant	17/17	1		ENSP00000447853.1	Q9H2H9
SLC38A1	ENST00000549049.5 linkuse as main transcript	c.1449T>A	p.Ser483Arg	missense_variant	16/16	1		ENSP00000449607.1	Q9H2H9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248542

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461262

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726940

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Sep 01, 2024

The c.1449T>A (p.S483R) alteration is located in exon 17 (coding exon 15) of the SLC38A1 gene. This alteration results from a T to A substitution at nucleotide position 1449, causing the serine (S) at amino acid position 483 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.77

DANN

Benign

0.27

DEOGEN2

Benign

0.063

T;T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.34

.;.;.;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.033

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.43

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.96

N;N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.58

T;T;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.11

MutPred

0.34

Gain of catalytic residue at A478 (P = 2e-04);Gain of catalytic residue at A478 (P = 2e-04);Gain of catalytic residue at A478 (P = 2e-04);Gain of catalytic residue at A478 (P = 2e-04);

MVP

0.068

MPC

0.62

ClinPred

0.013

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.028

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