Variant X-116437840-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000598581.3(SLC6A14):c.99T>G(p.Asn33Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,206,644 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 76 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00017 ( 0 hom. 74 hem. )

Consequence

SLC6A14
ENST00000598581.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.180

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06742734).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A14	NM_007231.5 linkuse as main transcript	c.99T>G	p.Asn33Lys	missense_variant	2/14	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.99T>G	p.Asn33Lys	missense_variant	2/14	1	NM_007231.5	ENSP00000470801	P1

Frequencies

GnomAD3 genomes

AF:

0.0000714

AC:

AN:

111973

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

34151

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000206

AC:

AN:

179541

Hom.:

AF XY:

0.000203

AC XY:

AN XY:

64129

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000378

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.000384

Gnomad OTH exome

AF:

0.000452

GnomAD4 exome

AF:

0.000173

AC:

189

AN:

1094671

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

360185

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.000173

Gnomad4 NFE exome

AF:

0.000191

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.0000714

AC:

AN:

111973

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

34151

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000164

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.000354

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

Sep 17, 2021

The c.99T>G (p.N33K) alteration is located in exon 2 (coding exon 2) of the SLC6A14 gene. This alteration results from a T to G substitution at nucleotide position 99, causing the asparagine (N) at amino acid position 33 to be replaced by a lysine (K). 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

Pathogenic

0.90

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.78

M_CAP

Benign

0.082

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.93

PrimateAI

Uncertain

0.75

Sift4G

Benign

0.088

Polyphen

0.92

Vest4

0.14

MutPred

0.35

Gain of ubiquitination at N33 (P = 0.0075);

MVP

0.74

ClinPred

0.20

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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