Variant X-116442749-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_007231.5(SLC6A14):c.409G>T(p.Ala137Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00018 in 1,178,741 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 84 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.00018 ( 0 hom. 79 hem. )

Consequence

SLC6A14
NM_007231.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25548893).

BP6

Variant X-116442749-G-T is Benign according to our data. Variant chrX-116442749-G-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A14	NM_007231.5 linkuse as main transcript	c.409G>T	p.Ala137Ser	missense_variant	4/14	ENST00000598581.3	NP_009162.1	Q9UN76B2R8J1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A14	ENST00000598581.3 linkuse as main transcript	c.409G>T	p.Ala137Ser	missense_variant	4/14	1	NM_007231.5	ENSP00000470801.1		Q9UN76

Frequencies

GnomAD3 genomes

AF:

0.000162

AC:

AN:

110769

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

33041

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000967

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000321

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000172

AC:

AN:

162444

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

52492

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000128

Gnomad NFE exome

AF:

0.000344

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000182

AC:

194

AN:

1067972

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

340288

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000326

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000497

Gnomad4 NFE exome

AF:

0.000223

Gnomad4 OTH exome

AF:

0.000156

GnomAD4 genome

AF:

0.000162

AC:

AN:

110769

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

33041

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000967

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000321

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.409G>T (p.A137S) alteration is located in exon 4 (coding exon 4) of the SLC6A14 gene. This alteration results from a G to T substitution at nucleotide position 409, causing the alanine (A) at amino acid position 137 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.56

Sift4G

Benign

0.082

Polyphen

0.092

Vest4

0.27

MVP

0.70

ClinPred

0.055

GERP RS

5.6

Varity_R

0.30

gMVP

0.61

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