8-86217510-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138817.3(SLC7A13):​c.1139G>A​(p.Arg380Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,597,544 control chromosomes in the GnomAD database, including 20,846 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 Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1783 hom., cov: 32)
Exomes 𝑓: 0.15 ( 19063 hom. )

Consequence

SLC7A13
NM_138817.3 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.16
Variant links:
Genes affected
SLC7A13 (HGNC:23092): (solute carrier family 7 member 13) Predicted to enable L-amino acid transmembrane transporter activity. Predicted to be involved in L-cystine transport; L-glutamate transmembrane transport; and aspartate transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0062551796).
BP6
Variant 8-86217510-C-T is Benign according to our data. Variant chr8-86217510-C-T is described in ClinVar as [Benign]. Clinvar id is 1600690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC7A13NM_138817.3 linkc.1139G>A p.Arg380Lys missense_variant 3/4 ENST00000297524.8 NP_620172.2 Q8TCU3-1
SLC7A13XM_011516867.3 linkc.1112G>A p.Arg371Lys missense_variant 3/4 XP_011515169.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC7A13ENST00000297524.8 linkc.1139G>A p.Arg380Lys missense_variant 3/41 NM_138817.3 ENSP00000297524.3 Q8TCU3-1
SLC7A13ENST00000419776.2 linkc.1112G>A p.Arg371Lys missense_variant 3/51 ENSP00000410982.2 Q8TCU3-2

Frequencies

GnomAD3 genomes
AF:
0.130
AC:
19709
AN:
151928
Hom.:
1778
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0559
Gnomad AMI
AF:
0.142
Gnomad AMR
AF:
0.177
Gnomad ASJ
AF:
0.195
Gnomad EAS
AF:
0.332
Gnomad SAS
AF:
0.321
Gnomad FIN
AF:
0.115
Gnomad MID
AF:
0.241
Gnomad NFE
AF:
0.133
Gnomad OTH
AF:
0.150
GnomAD3 exomes
AF:
0.181
AC:
42933
AN:
237322
Hom.:
4872
AF XY:
0.186
AC XY:
23937
AN XY:
128546
show subpopulations
Gnomad AFR exome
AF:
0.0559
Gnomad AMR exome
AF:
0.237
Gnomad ASJ exome
AF:
0.192
Gnomad EAS exome
AF:
0.330
Gnomad SAS exome
AF:
0.317
Gnomad FIN exome
AF:
0.117
Gnomad NFE exome
AF:
0.135
Gnomad OTH exome
AF:
0.171
GnomAD4 exome
AF:
0.148
AC:
213757
AN:
1445498
Hom.:
19063
Cov.:
31
AF XY:
0.154
AC XY:
110429
AN XY:
718832
show subpopulations
Gnomad4 AFR exome
AF:
0.0507
Gnomad4 AMR exome
AF:
0.228
Gnomad4 ASJ exome
AF:
0.191
Gnomad4 EAS exome
AF:
0.324
Gnomad4 SAS exome
AF:
0.318
Gnomad4 FIN exome
AF:
0.118
Gnomad4 NFE exome
AF:
0.128
Gnomad4 OTH exome
AF:
0.159
GnomAD4 genome
AF:
0.130
AC:
19725
AN:
152046
Hom.:
1783
Cov.:
32
AF XY:
0.134
AC XY:
9931
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0558
Gnomad4 AMR
AF:
0.177
Gnomad4 ASJ
AF:
0.195
Gnomad4 EAS
AF:
0.333
Gnomad4 SAS
AF:
0.322
Gnomad4 FIN
AF:
0.115
Gnomad4 NFE
AF:
0.133
Gnomad4 OTH
AF:
0.151
Alfa
AF:
0.143
Hom.:
4373
Bravo
AF:
0.128
TwinsUK
AF:
0.130
AC:
483
ALSPAC
AF:
0.120
AC:
461
ESP6500AA
AF:
0.0565
AC:
248
ESP6500EA
AF:
0.127
AC:
1088
ExAC
AF:
0.179
AC:
21712
Asia WGS
AF:
0.327
AC:
1134
AN:
3474

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
0.73
DANN
Benign
0.36
DEOGEN2
Benign
0.070
T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.50
T;T
MetaRNN
Benign
0.0063
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-1.1
N;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
1.2
N;N
REVEL
Benign
0.16
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.038
MPC
0.0083
ClinPred
0.0014
T
GERP RS
-0.76
Varity_R
0.041
gMVP
0.30

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: rs4419794; hg19: chr8-87229739; COSMIC: COSV52534112; COSMIC: COSV52534112; API