Variant chr16-68290452-C-T 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_003983.6(SLC7A6):c.706C>T(p.Leu236Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000113 in 1,614,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

SLC7A6
NM_003983.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

Variant links:

Genes affected

SLC7A6 (HGNC:11064): (solute carrier family 7 member 6) Enables basic amino acid transmembrane transporter activity. Involved in basic amino acid transmembrane transport and ornithine transport. Located in intracellular membrane-bounded organelle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A6 links:

ENSG00000279649 (HGNC:):

ENSG00000279649 links:

SLC7A6OS (HGNC:25807): (solute carrier family 7 member 6 opposite strand) Predicted to be involved in developmental process. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in cytoplasm and nucleus. Implicated in progressive myoclonus epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A6OS 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=0.03759396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A6	NM_003983.6 linkuse as main transcript	c.706C>T	p.Leu236Phe	missense_variant	5/11	ENST00000219343.11	NP_003974.3	Q92536A0A024R719
SLC7A6	NM_001076785.3 linkuse as main transcript	c.706C>T	p.Leu236Phe	missense_variant	6/12		NP_001070253.1	Q92536A0A024R719

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A6	ENST00000219343.11 linkuse as main transcript	c.706C>T	p.Leu236Phe	missense_variant	5/11	1	NM_003983.6	ENSP00000219343.6		Q92536

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000135

AC:

AN:

251490

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000602

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00248

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000617

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00221

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.000778

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

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

Nov 27, 2024

The c.706C>T (p.L236F) alteration is located in exon 6 (coding exon 3) of the SLC7A6 gene. This alteration results from a C to T substitution at nucleotide position 706, causing the leucine (L) at amino acid position 236 to be replaced by a phenylalanine (F). 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

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;D

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

.;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.038

T;T

MetaSVM

Uncertain

0.45

MutationAssessor

Benign

1.2

L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.2

N;N

REVEL

Uncertain

0.47

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.91

P;P

Vest4

0.37

MVP

0.92

MPC

0.89

ClinPred

0.14

GERP RS

4.8

Varity_R

0.47

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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