Genetic Variant SLC7A13:p.Ser397Pro (chr8-86214637-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138817.3(SLC7A13):c.1189T>C(p.Ser397Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000386 in 1,606,100 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 4 hom. )

Consequence

SLC7A13
NM_138817.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.94

Publications

4 publications found

Variant links:

Genes affected

SLC7A13 (HGNC:23092): (solute carrier family 7 member 13) Predicted to enable L-amino acid transmembrane transporter activity. Predicted to be involved in L-cystine transport; L-glutamate transmembrane transport; and aspartate transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004819691).

BP6

Variant 8-86214637-A-G is Benign according to our data. Variant chr8-86214637-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2055187.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138817.3. 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
	SLC7A13	NM_138817.3	MANE Select	c.1189T>C	p.Ser397Pro	missense	Exon 4 of 4	NP_620172.2	Q8TCU3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A13	ENST00000297524.8	TSL:1 MANE Select	c.1189T>C	p.Ser397Pro	missense	Exon 4 of 4	ENSP00000297524.3	Q8TCU3-1
	SLC7A13	ENST00000419776.2	TSL:1	c.1290T>C	p.Cys430Cys	synonymous	Exon 5 of 5	ENSP00000410982.2	Q8TCU3-2

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

170

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00359

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000303

AC:

AN:

244278

AF XY:

0.000159

show subpopulations

Gnomad AFR exome

AF:

0.00397

Gnomad AMR exome

AF:

0.0000910

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000362

Gnomad OTH exome

AF:

0.000504

GnomAD4 exome

AF:

0.000303

AC:

440

AN:

1453754

Hom.:

Cov.:

AF XY:

0.000313

AC XY:

226

AN XY:

722590

show subpopulations

African (AFR)

AF:

0.00503

AC:

166

AN:

32974

American (AMR)

AF:

0.0000928

AC:

AN:

43096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25814

East Asian (EAS)

AF:

0.00

AC:

AN:

39482

South Asian (SAS)

AF:

0.0000586

AC:

AN:

85298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53254

Middle Eastern (MID)

AF:

0.00227

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.000173

AC:

192

AN:

1108112

Other (OTH)

AF:

0.00100

AC:

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00118

AC:

180

AN:

152346

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00382

AC:

159

AN:

41584

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68028

Other (OTH)

AF:

0.00189

AC:

AN:

2116

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

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:

0.000574

Hom.:

Bravo

AF:

0.00126

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000445

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.000220

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

8.6

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.069

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.18

M_CAP

Benign

0.051

MetaRNN

Benign

0.0048

MetaSVM

Benign

-0.75

PhyloP100

2.9

PrimateAI

Benign

0.28

PROVEAN

Benign

2.8

REVEL

Benign

0.21

Sift

Benign

0.92

Sift4G

Benign

0.91

Polyphen

0.0010

Vest4

0.093

MVP

0.24

MPC

0.0079

ClinPred

0.013

GERP RS

4.3

Varity_R

0.045

gMVP

0.45

Mutation Taster

=99/1

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

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