chr16-58671102-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018231.3(SLC38A7):​c.1174G>A​(p.Gly392Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,613,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SLC38A7
NM_018231.3 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75
Variant links:
Genes affected
SLC38A7 (HGNC:25582): (solute carrier family 38 member 7) Predicted to enable L-amino acid transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and sodium ion transport. Predicted to be located in axon and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC38A7NM_018231.3 linkc.1174G>A p.Gly392Ser missense_variant Exon 10 of 12 ENST00000219320.9 NP_060701.1 Q9NVC3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC38A7ENST00000219320.9 linkc.1174G>A p.Gly392Ser missense_variant Exon 10 of 12 1 NM_018231.3 ENSP00000219320.3 Q9NVC3-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152112
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000523
AC:
13
AN:
248456
Hom.:
0
AF XY:
0.0000668
AC XY:
9
AN XY:
134662
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000581
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.0000473
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461542
Hom.:
0
Cov.:
33
AF XY:
0.0000275
AC XY:
20
AN XY:
727064
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000186
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152112
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 14, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1174G>A (p.G392S) alteration is located in exon 10 (coding exon 8) of the SLC38A7 gene. This alteration results from a G to A substitution at nucleotide position 1174, causing the glycine (G) at amino acid position 392 to be replaced by a serine (S). 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
0.31
BayesDel_addAF
Benign
-0.097
T
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.021
T;T;T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.92
.;D;D
M_CAP
Benign
0.026
D
MetaRNN
Pathogenic
0.81
D;D;D
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.91
L;L;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.7
N;N;N
REVEL
Uncertain
0.36
Sift
Benign
0.72
T;T;T
Sift4G
Benign
0.51
T;T;T
Polyphen
1.0
D;D;.
Vest4
0.87
MutPred
0.80
Loss of ubiquitination at K393 (P = 0.0755);Loss of ubiquitination at K393 (P = 0.0755);.;
MVP
0.66
MPC
0.99
ClinPred
0.44
T
GERP RS
5.7
Varity_R
0.28
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs761106367; hg19: chr16-58705006; COSMIC: COSV54703691; COSMIC: COSV54703691; API