Variant X-116445006-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000598581.3(SLC6A14):c.745A>G(p.Ile249Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000827 in 1,207,196 control chromosomes in the GnomAD database, including 5 homozygotes. There are 277 hemizygotes in GnomAD. 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 0.0040 ( 0 hom., 131 hem., cov: 22)

Exomes 𝑓: 0.00051 ( 5 hom. 146 hem. )

Consequence

SLC6A14
ENST00000598581.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.20

Variant links:

Genes affected

SLC6A14 (HGNC:11047): (solute carrier family 6 member 14) This gene encodes a member of the solute carrier family 6. Members of this family are sodium and chloride dependent neurotransmitter transporters. The encoded protein transports both neutral and cationic amino acids. This protein may also function as a beta-alanine carrier. Mutations in this gene may be associated with X-linked obesity. A pseudogene of this gene is found on chromosome X.[provided by RefSeq, May 2010]

SLC6A14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008882105).

BP6

Variant X-116445006-A-G is Benign according to our data. Variant chrX-116445006-A-G is described in ClinVar as [Benign]. Clinvar id is 786395.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 131 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A14	NM_007231.5 linkuse as main transcript	c.745A>G	p.Ile249Val	missense_variant	6/14	ENST00000598581.3	NP_009162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A14	ENST00000598581.3 linkuse as main transcript	c.745A>G	p.Ile249Val	missense_variant	6/14	1	NM_007231.5	ENSP00000470801	P1

Frequencies

GnomAD3 genomes

AF:

0.00393

AC:

438

AN:

111498

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

128

AN XY:

33708

show subpopulations

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00153

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000166

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00121

AC:

215

AN:

178119

Hom.:

AF XY:

0.000619

AC XY:

AN XY:

62987

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.000907

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000331

Gnomad FIN exome

AF:

0.0000632

Gnomad NFE exome

AF:

0.0000376

Gnomad OTH exome

AF:

0.000690

GnomAD4 exome

AF:

0.000507

AC:

555

AN:

1095647

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

146

AN XY:

361355

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.000223

Gnomad4 FIN exome

AF:

0.0000988

Gnomad4 NFE exome

AF:

0.0000321

Gnomad4 OTH exome

AF:

0.00115

GnomAD4 genome

AF:

0.00397

AC:

443

AN:

111549

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

131

AN XY:

33769

show subpopulations

Gnomad4 AFR

AF:

0.0137

Gnomad4 AMR

AF:

0.00153

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000166

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00330

Alfa

AF:

0.000910

Hom.:

Bravo

AF:

0.00449

ESP6500AA

AF:

0.0120

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00133

AC:

162

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

Labcorp Genetics (formerly Invitae), Labcorp

Jun 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0089

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.95

PrimateAI

Benign

0.47

Sift4G

Benign

0.54

Polyphen

0.15

Vest4

0.45

MVP

0.47

ClinPred

0.022

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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