Variant 8-86217552-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138817.3(SLC7A13):c.1097C>T(p.Thr366Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 1,612,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

SLC7A13
NM_138817.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.776

Variant links:

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]

SLC7A13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03329003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A13	NM_138817.3 linkuse as main transcript	c.1097C>T	p.Thr366Met	missense_variant	3/4	ENST00000297524.8	NP_620172.2	Q8TCU3-1
SLC7A13	XM_011516867.3 linkuse as main transcript	c.1070C>T	p.Thr357Met	missense_variant	3/4		XP_011515169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A13	ENST00000297524.8 linkuse as main transcript	c.1097C>T	p.Thr366Met	missense_variant	3/4	1	NM_138817.3	ENSP00000297524.3		Q8TCU3-1
SLC7A13	ENST00000419776.2 linkuse as main transcript	c.1070C>T	p.Thr357Met	missense_variant	3/5	1		ENSP00000410982.2		Q8TCU3-2

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000105

AC:

AN:

248724

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

134732

show subpopulations

Gnomad AFR exome

AF:

0.0000636

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000430

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.0000710

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000877

AC:

128

AN:

1460130

Hom.:

Cov.:

AF XY:

0.0000950

AC XY:

AN XY:

726354

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.0000898

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000453

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000585

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2021

The c.1097C>T (p.T366M) alteration is located in exon 3 (coding exon 3) of the SLC7A13 gene. This alteration results from a C to T substitution at nucleotide position 1097, causing the threonine (T) at amino acid position 366 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.15

DANN

Benign

0.82

DEOGEN2

Benign

0.084

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.10

N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

0.14

N;N

REVEL

Benign

0.17

Sift

Benign

0.12

T;D

Sift4G

Benign

0.24

T;T

Polyphen

0.23

B;P

Vest4

0.046

MVP

0.19

MPC

0.0089

ClinPred

0.018

GERP RS

-2.6

Varity_R

0.021

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over