NM_138817.3:c.1408G>A

Variant names:

• chr8-86214418-C-T
• rs9693999
• NM_138817.3:c.1408G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E470G) has been classified as Uncertain significance.

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.71
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1603156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A13	NM_138817.3	MANE Select	c.1408G>A	p.Glu470Lys	missense	Exon 4 of 4	NP_620172.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A13	ENST00000297524.8	TSL:1 MANE Select	c.1408G>A	p.Glu470Lys	missense	Exon 4 of 4	ENSP00000297524.3
	SLC7A13	ENST00000419776.2	TSL:1	c.*207G>A		3_prime_UTR	Exon 5 of 5	ENSP00000410982.2

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

GnomAD2 exomes AF: 0.00896 AC: 2158 AN: 240772 AF XY: 0.00713

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 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

African (AFR) AF: 0.112 AC: 3697 AN: 32904

American (AMR) AF: 0.00647 AC: 284 AN: 43870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39422

South Asian (SAS) AF: 0.00553 AC: 471 AN: 85230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49696

Middle Eastern (MID) AF: 0.00684 AC: 39 AN: 5698

European-Non Finnish (NFE) AF: 0.000419 AC: 462 AN: 1101906

Other (OTH) AF: 0.00818 AC: 489 AN: 59802

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

African (AFR) AF: 0.107 AC: 4456 AN: 41494

American (AMR) AF: 0.0138 AC: 210 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000574 AC: 39 AN: 68002

Other (OTH) AF: 0.0265 AC: 56 AN: 2114

Alfa AF: 0.0115 Hom.: 177

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.7
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9693999; hg19: chr8-87226647;