rs9693999

chr8-86214418-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138817.3(SLC7A13):c.1408G>A(p.Glu470Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00642 in 1,596,532 control chromosomes in the GnomAD database, including 486 homozygotes. 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 Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.032 (270 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (216 hom.)
• Consequence: SLC7A13 NM_138817.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.71

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017810166).
• BP6: Variant 8-86214418-C-T is Benign according to our data. Variant chr8-86214418-C-T is described in ClinVar as [Benign]. Clinvar id is 1603156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A13	NM_138817.3	c.1408G>A	p.Glu470Lys	missense_variant	4/4	ENST00000297524.8
SLC7A13	XM_011516867.3	c.1381G>A	p.Glu461Lys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A13	ENST00000297524.8	c.1408G>A	p.Glu470Lys	missense_variant	4/4	1	NM_138817.3	P1
SLC7A13	ENST00000419776.2	c.*207G>A		3_prime_UTR_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4780 AN: 152030 Hom.: 270 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.00896 AC: 2158 AN: 240772 Hom.: 103 AF XY: 0.00713 AC XY: 933 AN XY: 130942

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.00570

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00581

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000370

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00377 AC: 5443 AN: 1444384 Hom.: 216 Cov.: 28 AF XY: 0.00347 AC XY: 2497 AN XY: 719310

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.00647

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00553

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000419

Gnomad4 OTH exome AF: 0.00818

GnomAD4 genome AF: 0.0316 AC: 4803 AN: 152148 Hom.: 270 Cov.: 33 AF XY: 0.0310 AC XY: 2304 AN XY: 74384

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000574

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.00542 Hom.: 79

Bravo AF: 0.0352

ESP6500AA AF: 0.0945 AC: 416

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.0106 AC: 1286

Asia WGS AF: 0.0150 AC: 52 AN: 3476

EpiCase AF: 0.000389

EpiControl AF: 0.000482

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	15
Dann	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.19	T
Sift4G	Uncertain	0.023	D
Polyphen		0.068	B
Vest4		0.10
MPC		0.0091
ClinPred		0.014	T
GERP RS		2.3
Varity_R		0.040
gMVP		0.35

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

Other links and lift over

dbSNP: rs9693999; hg19: chr8-87226647;