Variant 12-46197779-A-C 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.1303T>G(p.Ser435Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000237 in 1,602,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

SLC38A1
NM_030674.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

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=0.054462075).

BS2

High AC in GnomAdExome4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A1	NM_030674.4 linkuse as main transcript	c.1303T>G	p.Ser435Ala	missense_variant	16/17	ENST00000398637.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A1	ENST00000398637.10 linkuse as main transcript	c.1303T>G	p.Ser435Ala	missense_variant	16/17	1	NM_030674.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000138

AC:

AN:

238304

Hom.:

AF XY:

0.0000541

AC XY:

AN XY:

129276

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00103

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:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1450544

Hom.:

Cov.:

AF XY:

0.00000832

AC XY:

AN XY:

721396

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000850

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.000157

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

Jul 08, 2022

The c.1303T>G (p.S435A) alteration is located in exon 16 (coding exon 14) of the SLC38A1 gene. This alteration results from a T to G substitution at nucleotide position 1303, causing the serine (S) at amino acid position 435 to be replaced by an alanine (A). 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

0.080

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.044

T;T;T;T;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.0036

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.75

.;.;.;T;.;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.054

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.73

N;N;N;N;.;.

MutationTaster

Benign

0.78

D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.10

N;N;N;N;N;.

REVEL

Benign

0.16

Sift

Benign

0.55

T;T;T;T;T;.

Sift4G

Benign

0.62

T;T;T;T;T;T

Polyphen

0.046

B;B;B;B;B;B

Vest4

0.55

MutPred

0.67

Gain of catalytic residue at L433 (P = 2e-04);Gain of catalytic residue at L433 (P = 2e-04);Gain of catalytic residue at L433 (P = 2e-04);Gain of catalytic residue at L433 (P = 2e-04);Gain of catalytic residue at L433 (P = 2e-04);Gain of catalytic residue at L433 (P = 2e-04);

MVP

0.11

MPC

1.1

ClinPred

0.071

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.081

gMVP

0.51

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