Variant 12-46188981-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_030674.4(SLC38A1):c.1453G>A(p.Glu485Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,612,948 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

SLC38A1
NM_030674.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.922

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012909621).

BS2

High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A1	NM_030674.4 linkuse as main transcript	c.1453G>A	p.Glu485Lys	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.1453G>A	p.Glu485Lys	missense_variant	17/17	1	NM_030674.4	ENSP00000381634.4	Q9H2H9
SLC38A1	ENST00000439706.5 linkuse as main transcript	c.1453G>A	p.Glu485Lys	missense_variant	18/18	1		ENSP00000398142.1	Q9H2H9
SLC38A1	ENST00000546893.5 linkuse as main transcript	c.1453G>A	p.Glu485Lys	missense_variant	17/17	1		ENSP00000447853.1	Q9H2H9
SLC38A1	ENST00000549049.5 linkuse as main transcript	c.1453G>A	p.Glu485Lys	missense_variant	16/16	1		ENSP00000449607.1	Q9H2H9

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000338

AC:

AN:

248224

Hom.:

AF XY:

0.000290

AC XY:

AN XY:

134708

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.000448

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00118

Gnomad NFE exome

AF:

0.000381

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000319

AC:

466

AN:

1461030

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

225

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.000454

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000886

Gnomad4 NFE exome

AF:

0.000327

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000230

AC:

AN:

151918

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00142

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.000397

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000297

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

Feb 05, 2024

The c.1453G>A (p.E485K) alteration is located in exon 17 (coding exon 15) of the SLC38A1 gene. This alteration results from a G to A substitution at nucleotide position 1453, causing the glutamic acid (E) at amino acid position 485 to be replaced by a lysine (K). 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

0.085

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.27

DEOGEN2

Benign

0.059

T;T;T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.55

.;.;.;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.013

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.29

N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.010

N;N;N;N

REVEL

Benign

0.030

Sift

Benign

0.80

T;T;T;T

Sift4G

Benign

0.97

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.16

MVP

0.093

MPC

0.63

ClinPred

0.0039

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

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