13-29523342-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003045.5(SLC7A1):​c.973G>A​(p.Asp325Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,613,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

SLC7A1
NM_003045.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82
Variant links:
Genes affected
SLC7A1 (HGNC:11057): (solute carrier family 7 member 1) Enables L-arginine transmembrane transporter activity and L-histidine transmembrane transporter activity. Involved in amino acid transport. Located in membrane. Part of apical plasma membrane; basolateral plasma membrane; and protein-containing complex. [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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12180057).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC7A1NM_003045.5 linkc.973G>A p.Asp325Asn missense_variant Exon 7 of 13 ENST00000380752.10 NP_003036.1 P30825A0A024RDQ9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC7A1ENST00000380752.10 linkc.973G>A p.Asp325Asn missense_variant Exon 7 of 13 1 NM_003045.5 ENSP00000370128.5 P30825

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
151996
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
251036
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135720
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000289
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:
0.0000176
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000363
AC:
53
AN:
1461598
Hom.:
0
Cov.:
33
AF XY:
0.0000385
AC XY:
28
AN XY:
727076
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000351
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000452
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.973G>A (p.D325N) alteration is located in exon 7 (coding exon 5) of the SLC7A1 gene. This alteration results from a G to A substitution at nucleotide position 973, causing the aspartic acid (D) at amino acid position 325 to be replaced by an asparagine (N). 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
0.085
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.58
D
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.68
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
1.2
L
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.70
N
REVEL
Benign
0.16
Sift
Benign
0.43
T
Sift4G
Benign
0.40
T
Polyphen
0.0030
B
Vest4
0.32
MutPred
0.30
Gain of methylation at K328 (P = 0.0797);
MVP
0.43
MPC
0.76
ClinPred
0.067
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.046
gMVP
0.30

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.

Other links and lift over

dbSNP: rs558871896; hg19: chr13-30097479; API