Genetic Variant SLC7A3:p.Phe209Cys (chrX-70928537-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032803.6(SLC7A3):c.626T>G(p.Phe209Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00012 in 1,204,397 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 10 hem., cov: 22)

Exomes 𝑓: 0.00011 ( 0 hom. 32 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Publications

1 publications found

Variant links:

Genes affected

SLC7A3 (HGNC:11061): (solute carrier family 7 member 3) This gene encodes a member of the solute carrier family 7. The encoded protein is a sodium-independent cationic amino acid transporter. Alternate splicing results in multiple transcripts that encoded the same protein.[provided by RefSeq, May 2010]

SLC7A3 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SLC7A3 links:

ENSG00000295939 (HGNC:):

ENSG00000295939 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11292094).

BS2

High AC in GnomAd4 at 28 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032803.6. 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
	SLC7A3	NM_032803.6	MANE Select	c.626T>G	p.Phe209Cys	missense	Exon 4 of 12	NP_116192.4
	SLC7A3	NM_001048164.3		c.626T>G	p.Phe209Cys	missense	Exon 4 of 12	NP_001041629.1	Q8WY07

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC7A3	ENST00000374299.8	TSL:1 MANE Select	c.626T>G	p.Phe209Cys	missense	Exon 4 of 12	ENSP00000363417.3	Q8WY07
SLC7A3	ENST00000921007.1		c.626T>G	p.Phe209Cys	missense	Exon 4 of 13	ENSP00000591066.1
SLC7A3	ENST00000921008.1		c.626T>G	p.Phe209Cys	missense	Exon 4 of 13	ENSP00000591067.1

Frequencies

GnomAD3 genomes

AF:

0.000253

AC:

AN:

110758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00115

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000843

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000229

AC:

AN:

170335

AF XY:

0.000177

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000419

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000673

Gnomad NFE exome

AF:

0.000214

Gnomad OTH exome

AF:

0.000465

GnomAD4 exome

AF:

0.000106

AC:

116

AN:

1093639

Hom.:

Cov.:

AF XY:

0.0000890

AC XY:

AN XY:

359575

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26356

American (AMR)

AF:

0.000289

AC:

AN:

34603

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19276

East Asian (EAS)

AF:

0.00

AC:

AN:

30136

South Asian (SAS)

AF:

0.00

AC:

AN:

53050

European-Finnish (FIN)

AF:

0.000769

AC:

AN:

40305

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000845

AC:

AN:

839812

Other (OTH)

AF:

0.0000870

AC:

AN:

45967

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000253

AC:

AN:

110758

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

AN XY:

32974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30453

American (AMR)

AF:

0.00115

AC:

AN:

10409

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3522

South Asian (SAS)

AF:

0.00

AC:

AN:

2559

European-Finnish (FIN)

AF:

0.000843

AC:

AN:

5931

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000208

AC:

AN:

52830

Other (OTH)

AF:

0.00

AC:

AN:

1491

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

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:

0.000270

Hom.:

Bravo

AF:

0.000344

ExAC

AF:

0.000280

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.11

MetaSVM

Uncertain

0.42

MutationAssessor

Pathogenic

3.1

PhyloP100

4.0

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.53

Sift

Benign

0.046

Sift4G

Benign

0.091

Polyphen

0.049

Vest4

0.34

MVP

0.82

MPC

1.1

ClinPred

0.28

GERP RS

3.7

Varity_R

0.71

gMVP

0.89

Mutation Taster

=83/17

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over