12-46239793-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_030674.4(SLC38A1):ā€‹c.8A>Cā€‹(p.His3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,650 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

SLC38A1
NM_030674.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10290858).
BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC38A1NM_030674.4 linkuse as main transcriptc.8A>C p.His3Pro missense_variant 3/17 ENST00000398637.10 NP_109599.3 Q9H2H9A0A024R124

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC38A1ENST00000398637.10 linkuse as main transcriptc.8A>C p.His3Pro missense_variant 3/171 NM_030674.4 ENSP00000381634.4 Q9H2H9

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249288
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135294
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.00000959
AC:
14
AN:
1460470
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
726562
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.00000756
ExAC
AF:
0.00000828
AC:
1

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 submitterclinical testingAmbry GeneticsNov 28, 2023The c.8A>C (p.H3P) alteration is located in exon 3 (coding exon 1) of the SLC38A1 gene. This alteration results from a A to C substitution at nucleotide position 8, causing the histidine (H) at amino acid position 3 to be replaced by a proline (P). 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
0.040
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Benign
0.068
T;T;T;T;.;.;.
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.054
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.70
.;.;.;T;.;T;T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.10
T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N;N;N;N;.;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-0.74
N;N;N;N;N;.;D
REVEL
Benign
0.047
Sift
Benign
0.16
T;T;T;T;T;.;T
Sift4G
Benign
0.65
T;T;T;T;T;T;.
Polyphen
0.0
B;B;B;B;B;B;.
Vest4
0.28
MutPred
0.29
Gain of catalytic residue at H3 (P = 0.0028);Gain of catalytic residue at H3 (P = 0.0028);Gain of catalytic residue at H3 (P = 0.0028);Gain of catalytic residue at H3 (P = 0.0028);Gain of catalytic residue at H3 (P = 0.0028);Gain of catalytic residue at H3 (P = 0.0028);Gain of catalytic residue at H3 (P = 0.0028);
MVP
0.043
MPC
0.87
ClinPred
0.28
T
GERP RS
5.1
Varity_R
0.22
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs373216951; hg19: chr12-46633576; API