dbSNP rs976272: SLC38A6:p.Leu70Met (chr14-60982610-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_153811.3(SLC38A6):c.208T>A(p.Leu70Met) variant causes a missense change. The variant allele was found at a frequency of 0.957 in 1,613,574 control chromosomes in the GnomAD database, including 742,354 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L70S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.93 ( 66617 hom., cov: 32)

Exomes 𝑓: 0.96 ( 675737 hom. )

Consequence

SLC38A6
NM_153811.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.84

Publications

28 publications found

Variant links:

Genes affected

SLC38A6 (HGNC:19863): (solute carrier family 38 member 6) Predicted to enable L-glutamine transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and glutamine transport. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC38A6 links:

ENSG00000258892 (HGNC:):

ENSG00000258892 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.409261E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A6	NM_153811.3 link	c.208T>A	p.Leu70Met	missense_variant	Exon 2 of 16	ENST00000267488.9	NP_722518.2	Q8IZM9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A6	ENST00000267488.9 link	c.208T>A	p.Leu70Met	missense_variant	Exon 2 of 16	1	NM_153811.3	ENSP00000267488.4		Q8IZM9-1

Frequencies

GnomAD3 genomes

AF:

0.933

AC:

141919

AN:

152148

Hom.:

66575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.885

Gnomad ASJ

AF:

0.948

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.777

Gnomad FIN

AF:

0.989

Gnomad MID

AF:

0.934

Gnomad NFE

AF:

0.987

Gnomad OTH

AF:

0.935

GnomAD2 exomes

AF:

0.917

AC:

230221

AN:

251022

AF XY:

0.918

show subpopulations

Gnomad AFR exome

AF:

0.882

Gnomad AMR exome

AF:

0.832

Gnomad ASJ exome

AF:

0.950

Gnomad EAS exome

AF:

0.782

Gnomad FIN exome

AF:

0.991

Gnomad NFE exome

AF:

0.986

Gnomad OTH exome

AF:

0.943

GnomAD4 exome

AF:

0.959

AC:

1401620

AN:

1461308

Hom.:

675737

Cov.:

AF XY:

0.955

AC XY:

694304

AN XY:

726894

show subpopulations

African (AFR)

AF:

0.881

AC:

29488

AN:

33462

American (AMR)

AF:

0.837

AC:

37355

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.950

AC:

24828

AN:

26128

East Asian (EAS)

AF:

0.723

AC:

28668

AN:

39668

South Asian (SAS)

AF:

0.794

AC:

68310

AN:

86070

European-Finnish (FIN)

AF:

0.991

AC:

52925

AN:

53410

Middle Eastern (MID)

AF:

0.949

AC:

5364

AN:

5650

European-Non Finnish (NFE)

AF:

0.987

AC:

1097311

AN:

1111928

Other (OTH)

AF:

0.950

AC:

57371

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

2515

5030

7546

10061

12576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21614

43228

64842

86456

108070

<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:

0.933

AC:

142021

AN:

152266

Hom.:

66617

Cov.:

AF XY:

0.928

AC XY:

69077

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.883

AC:

36676

AN:

41526

American (AMR)

AF:

0.885

AC:

13535

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.948

AC:

3291

AN:

3472

East Asian (EAS)

AF:

0.767

AC:

3965

AN:

5172

South Asian (SAS)

AF:

0.779

AC:

3760

AN:

4826

European-Finnish (FIN)

AF:

0.989

AC:

10501

AN:

10614

Middle Eastern (MID)

AF:

0.939

AC:

276

AN:

294

European-Non Finnish (NFE)

AF:

0.987

AC:

67139

AN:

68042

Other (OTH)

AF:

0.931

AC:

1966

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

447

893

1340

1786

2233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.974

Hom.:

18506

Bravo

AF:

0.925

TwinsUK

AF:

0.988

AC:

3662

ALSPAC

AF:

0.986

AC:

3799

ESP6500AA

AF:

0.873

AC:

3846

ESP6500EA

AF:

0.984

AC:

8460

ExAC

AF:

0.918

AC:

111508

Asia WGS

AF:

0.769

AC:

2675

AN:

3478

EpiCase

AF:

0.984

EpiControl

AF:

0.985

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.062

.;T;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.57

T;T;T;T

MetaRNN

Benign

5.4e-7

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

N;N;.;.

PhyloP100

6.8

PrimateAI

Uncertain

0.51

PROVEAN

Benign

2.7

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.012

B;B;.;.

Vest4

0.071

MPC

0.017

ClinPred

0.015

GERP RS

4.5

PromoterAI

-0.0076

Neutral

(source)

Varity_R

0.19

gMVP

0.49

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over