X-70928535-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_032803.6(SLC7A3):​c.628G>A​(p.Val210Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,204,339 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000018 ( 0 hom. 3 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

1
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.861
Variant links:
Genes affected
SLC7A3 (HGNC:11061): (solute carrier family 7 member 3) This gene encodes a member of the solute carrier family 7. The encoded protein is a sodium-independent cationic amino acid transporter. Alternate splicing results in multiple transcripts that encoded the same protein.[provided by RefSeq, May 2010]

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=0.113771915).
BP6
Variant X-70928535-C-T is Benign according to our data. Variant chrX-70928535-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3771600.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC7A3NM_032803.6 linkc.628G>A p.Val210Ile missense_variant Exon 4 of 12 ENST00000374299.8 NP_116192.4 Q8WY07
SLC7A3NM_001048164.3 linkc.628G>A p.Val210Ile missense_variant Exon 4 of 12 NP_001041629.1 Q8WY07
SLC7A3XM_047442598.1 linkc.628G>A p.Val210Ile missense_variant Exon 3 of 11 XP_047298554.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC7A3ENST00000374299.8 linkc.628G>A p.Val210Ile missense_variant Exon 4 of 12 1 NM_032803.6 ENSP00000363417.3 Q8WY07
SLC7A3ENST00000298085.4 linkc.628G>A p.Val210Ile missense_variant Exon 4 of 12 2 ENSP00000298085.4 Q8WY07

Frequencies

GnomAD3 genomes
AF:
0.0000270
AC:
3
AN:
111040
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33234
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000191
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00424
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000183
AC:
20
AN:
1093245
Hom.:
0
Cov.:
32
AF XY:
0.00000835
AC XY:
3
AN XY:
359279
show subpopulations
Gnomad4 AFR exome
AF:
0.0000760
Gnomad4 AMR exome
AF:
0.0000289
Gnomad4 ASJ exome
AF:
0.0000519
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000143
Gnomad4 OTH exome
AF:
0.0000870
GnomAD4 genome
AF:
0.0000270
AC:
3
AN:
111094
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33298
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000191
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
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Dec 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

SLC7A3: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
9.9
DANN
Benign
0.50
DEOGEN2
Benign
0.16
T;T
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.67
.;T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
-0.94
N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
0.15
N;N
REVEL
Benign
0.22
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.072
MutPred
0.40
Loss of methylation at K211 (P = 0.0583);Loss of methylation at K211 (P = 0.0583);
MVP
0.28
MPC
0.27
ClinPred
0.56
D
GERP RS
2.6
Varity_R
0.063
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs774144802; hg19: chrX-70148385; COSMIC: COSV105139688; API