Genetic Variant SLC7A6:p.Glu26Asp (chr16-68274804-A-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

4 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003983.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A6	NM_003983.6	MANE Select	c.78A>T	p.Glu26Asp	missense	Exon 3 of 11	NP_003974.3	Q92536
	SLC7A6	NM_001076785.3		c.78A>T	p.Glu26Asp	missense	Exon 4 of 12	NP_001070253.1	Q92536

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC7A6	ENST00000219343.11	TSL:1 MANE Select	c.78A>T	p.Glu26Asp	missense	Exon 3 of 11	ENSP00000219343.6	Q92536
SLC7A6	ENST00000379152.7	TSL:1	n.78A>T		non_coding_transcript_exon	Exon 3 of 11	ENSP00000368448.3	E7EPZ8
SLC7A6	ENST00000566454.5	TSL:5	c.78A>T	p.Glu26Asp	missense	Exon 4 of 12	ENSP00000455064.1	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

GnomAD2 exomes

AF:

0.0104

AC:

2607

AN:

251468

AF XY:

0.00833

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 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

African (AFR)

AF:

0.000269

AC:

AN:

33480

American (AMR)

AF:

0.0476

AC:

2131

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0251

AC:

997

AN:

39698

South Asian (SAS)

AF:

0.000522

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.0101

AC:

539

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000150

AC:

167

AN:

1111974

Other (OTH)

AF:

0.00252

AC:

152

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

289

578

866

1155

1444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00604

AC:

920

AN:

152304

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

540

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41576

American (AMR)

AF:

0.0388

AC:

593

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0253

AC:

131

AN:

5178

South Asian (SAS)

AF:

0.00187

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0120

AC:

127

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

68038

Other (OTH)

AF:

0.00617

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

135

180

225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SLC7A6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.0

PhyloP100

2.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.0

REVEL

Benign

0.23

Sift

Benign

0.46

Sift4G

Benign

0.29

Polyphen

0.044

Vest4

0.19

MutPred

0.14

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

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over