Variant chr5-150190335-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014228.5(SLC6A7):c.8A>G(p.Lys3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,508,540 control chromosomes in the GnomAD database, including 9 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 9 hom. )

Consequence

SLC6A7
NM_014228.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.455

Variant links:

Genes affected

SLC6A7 (HGNC:11054): (solute carrier family 6 member 7) This gene is a member of the gamma-aminobutyric acid (GABA) neurotransmitter gene family and encodes a high-affinity mammalian brain L-proline transporter protein. This transporter protein differs from other sodium-dependent plasma membrane carriers by its pharmacological specificity, kinetic properties, and ionic requirements. [provided by RefSeq, Jul 2008]

SLC6A7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004055202).

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A7	NM_014228.5 linkuse as main transcript	c.8A>G	p.Lys3Arg	missense_variant	1/14	ENST00000230671.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC6A7	ENST00000230671.7 linkuse as main transcript	c.8A>G	p.Lys3Arg	missense_variant	1/14	1	NM_014228.5	P1
SLC6A7	ENST00000524041.1 linkuse as main transcript	c.8A>G	p.Lys3Arg	missense_variant	1/16	5
SLC6A7	ENST00000513403.1 linkuse as main transcript	n.85A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00203

AC:

308

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00340

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00170

AC:

177

AN:

103832

Hom.:

AF XY:

0.00161

AC XY:

AN XY:

57676

show subpopulations

Gnomad AFR exome

AF:

0.000415

Gnomad AMR exome

AF:

0.00245

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000540

Gnomad FIN exome

AF:

0.000341

Gnomad NFE exome

AF:

0.00271

Gnomad OTH exome

AF:

0.00426

GnomAD4 exome

AF:

0.00279

AC:

3782

AN:

1356392

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

1825

AN XY:

668924

show subpopulations

Gnomad4 AFR exome

AF:

0.000580

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00250

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000399

Gnomad4 FIN exome

AF:

0.000444

Gnomad4 NFE exome

AF:

0.00325

Gnomad4 OTH exome

AF:

0.00249

GnomAD4 genome

AF:

0.00202

AC:

308

AN:

152148

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00340

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00282

Hom.:

Bravo

AF:

0.00201

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00142

AC:

ExAC

AF:

0.000719

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.12

Sift

Benign

0.25

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0

B;.

Vest4

0.062

MVP

0.41

MPC

0.15

ClinPred

0.0055

GERP RS

1.4

Varity_R

0.064

gMVP

0.14

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