Variant chr12-221456-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016615.5(SLC6A13):c.1606C>T(p.Leu536Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,674 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 1 hom. )

Consequence

SLC6A13
NM_016615.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

Variant links:

Genes affected

SLC6A13 (HGNC:11046): (solute carrier family 6 member 13) Enables amino acid transmembrane transporter activity and monocarboxylic acid transmembrane transporter activity. Involved in amino acid import across plasma membrane and monocarboxylic acid transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SLC6A13 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27257848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A13	NM_016615.5 linkuse as main transcript	c.1606C>T	p.Leu536Phe	missense_variant	14/15	ENST00000343164.9	NP_057699.2	Q9NSD5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A13	ENST00000343164.9 linkuse as main transcript	c.1606C>T	p.Leu536Phe	missense_variant	14/15	1	NM_016615.5	ENSP00000339260.4		Q9NSD5-1
SLC6A13	ENST00000445055.6 linkuse as main transcript	c.1330C>T	p.Leu444Phe	missense_variant	12/13	2		ENSP00000407104.2		Q9NSD5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250938

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135710

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:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 01, 2024

The c.1606C>T (p.L536F) alteration is located in exon 14 (coding exon 13) of the SLC6A13 gene. This alteration results from a C to T substitution at nucleotide position 1606, causing the leucine (L) at amino acid position 536 to be replaced by a phenylalanine (F). 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

0.082

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.030

.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.59

.;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.14

Sift

Benign

0.64

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0

.;B

Vest4

0.34

MutPred

0.71

.;Gain of helix (P = 0.132);

MVP

0.78

MPC

0.092

ClinPred

0.083

GERP RS

4.3

Varity_R

0.12

gMVP

0.73

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