NM_003983.6:c.78A>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003983.6(SLC7A6):c.78A>T(p.Glu26Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,614,138 control chromosomes in the GnomAD database, including 100 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 (no stars).

Frequency

Genomes: 𝑓 0.0060 ( 28 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 72 hom. )

Consequence

SLC7A6
NM_003983.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025736094).

BP6

Variant 16-68274804-A-T is Benign according to our data. Variant chr16-68274804-A-T is described in ClinVar as [Benign]. Clinvar id is 3059041.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00604 (920/152304) while in subpopulation AMR AF= 0.0388 (593/15284). AF 95% confidence interval is 0.0362. There are 28 homozygotes in gnomad4. There are 540 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A6	NM_003983.6 link	c.78A>T	p.Glu26Asp	missense_variant	Exon 3 of 11	ENST00000219343.11	NP_003974.3	Q92536A0A024R719
SLC7A6	NM_001076785.3 link	c.78A>T	p.Glu26Asp	missense_variant	Exon 4 of 12		NP_001070253.1	Q92536A0A024R719

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A6	ENST00000219343.11 link	c.78A>T	p.Glu26Asp	missense_variant	Exon 3 of 11	1	NM_003983.6	ENSP00000219343.6		Q92536

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

914

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0385

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0252

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.0104

AC:

2607

AN:

251468

Hom.:

AF XY:

0.00833

AC XY:

1132

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0506

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0277

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00733

GnomAD4 exome

AF:

0.00276

AC:

4041

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

1851

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0476

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0251

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00604

AC:

920

AN:

152304

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

540

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0388

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0253

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00152

Hom.:

Bravo

AF:

0.00707

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00781

AC:

948

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC7A6-related disorder

Benign:1

Nov 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0050

T;T;T;T;.;T;T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.58

T;.;T;T;T;T;T;T

MetaRNN

Benign

0.0026

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.0

.;N;.;N;.;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.0

.;N;D;N;D;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.46

.;T;D;T;.;T;T;T

Sift4G

Benign

0.29

T;T;D;T;.;T;T;T

Polyphen

0.044

.;B;.;B;.;.;.;.

Vest4

0.19

MutPred

0.14

Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);

MPC

0.42

ClinPred

0.0068

GERP RS

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.068

gMVP

0.17

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