Variant 3-14447599-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003043.6(SLC6A6):c.382G>A(p.Val128Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,614,172 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 26 hom., cov: 33)

Exomes 𝑓: 0.011 ( 172 hom. )

Consequence

SLC6A6
NM_003043.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.01

Variant links:

Genes affected

SLC6A6 (HGNC:11052): (solute carrier family 6 member 6) This gene encodes a multi-pass membrane protein that is a member of a family of sodium and chloride-ion dependent transporters. The encoded protein transports taurine and beta-alanine. There is a pseudogene for this gene on chromosome 21. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

SLC6A6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041282177).

BP6

Variant 3-14447599-G-A is Benign according to our data. Variant chr3-14447599-G-A is described in ClinVar as [Benign]. Clinvar id is 3234140.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A6	NM_003043.6 link	c.382G>A	p.Val128Ile	missense_variant	5/15	ENST00000622186.5	NP_003034.2	P31641-1B4E140Q59GD7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A6	ENST00000622186.5 link	c.382G>A	p.Val128Ile	missense_variant	5/15	1	NM_003043.6	ENSP00000480890.1		P31641-1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1648

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00910

Gnomad FIN

AF:

0.0584

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.0121

AC:

3048

AN:

250906

Hom.:

AF XY:

0.0122

AC XY:

1655

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00509

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00990

Gnomad FIN exome

AF:

0.0570

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0107

AC:

15705

AN:

1461848

Hom.:

172

Cov.:

AF XY:

0.0106

AC XY:

7741

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00512

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0570

Gnomad4 NFE exome

AF:

0.00975

Gnomad4 OTH exome

AF:

0.00927

GnomAD4 genome

AF:

0.0108

AC:

1650

AN:

152324

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

968

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00932

Gnomad4 FIN

AF:

0.0584

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00934

Hom.:

Bravo

AF:

0.00628

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.0121

AC:

1474

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00859

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

SLC6A6: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.045

N;.;N

PrimateAI

Uncertain

0.76

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.063

ClinPred

0.0063

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.067

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