12-223160-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016615.5(SLC6A13):c.1386C>A(p.Phe462Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC6A13 NM_016615.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.755

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A13	NM_016615.5	c.1386C>A	p.Phe462Leu	missense_variant	12/15	ENST00000343164.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A13	ENST00000343164.9	c.1386C>A	p.Phe462Leu	missense_variant	12/15	1	NM_016615.5	P1
SLC6A13	ENST00000445055.6	c.1110C>A	p.Phe370Leu	missense_variant	10/13	2
SLC6A13	ENST00000539668.1	n.344C>A		non_coding_transcript_exon_variant	4/5	5
SLC6A13	ENST00000542379.1	n.294C>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.1386C>A (p.F462L) alteration is located in exon 12 (coding exon 11) of the SLC6A13 gene. This alteration results from a C to A substitution at nucleotide position 1386, causing the phenylalanine (F) at amino acid position 462 to be replaced by a leucine (L). 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	0.86
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.65	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.47
Sift	Benign	0.055	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.41	.;B
Vest4		0.77
MutPred		0.63		.;Loss of catalytic residue at F462 (P = 0.3005);
MVP		0.70
MPC		0.17
ClinPred		0.97	D
GERP RS		1.1
Varity_R		0.60
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-332326;