chr8-86214417-T-C

Position:

• chr8-86214417-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138817.3(SLC7A13):​c.1409A>G​(p.Glu470Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E470K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC7A13 NM_138817.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92

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 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=0.21731946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A13	NM_138817.3	c.1409A>G	p.Glu470Gly	missense_variant	4/4	ENST00000297524.8	NP_620172.2
SLC7A13	XM_011516867.3	c.1382A>G	p.Glu461Gly	missense_variant	4/4		XP_011515169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A13	ENST00000297524.8	c.1409A>G	p.Glu470Gly	missense_variant	4/4	1	NM_138817.3	ENSP00000297524.3
SLC7A13	ENST00000419776	c.*208A>G		3_prime_UTR_variant	5/5	1		ENSP00000410982.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441140 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 717792

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.09e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 23, 2025

This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 470 of the SLC7A13 protein (p.Glu470Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC7A13-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	-0.086	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.010	D
Polyphen		0.65	P
Vest4		0.20
MutPred		0.31		Loss of stability (P = 0.026);
MVP		0.44
MPC		0.028
ClinPred		0.89	D
GERP RS		4.2
Varity_R		0.12
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-87226646;