12-222566-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016615.5(SLC6A13):c.1481A>C(p.Tyr494Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 2.23

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A13	NM_016615.5	c.1481A>C	p.Tyr494Ser	missense_variant	13/15	ENST00000343164.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A13	ENST00000343164.9	c.1481A>C	p.Tyr494Ser	missense_variant	13/15	1	NM_016615.5	P1
SLC6A13	ENST00000445055.6	c.1205A>C	p.Tyr402Ser	missense_variant	11/13	2
SLC6A13	ENST00000539668.1			downstream_gene_variant		5

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 18, 2022

The c.1481A>C (p.Y494S) alteration is located in exon 13 (coding exon 12) of the SLC6A13 gene. This alteration results from a A to C substitution at nucleotide position 1481, causing the tyrosine (Y) at amino acid position 494 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	0.24
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Uncertain	-0.026	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.61
Sift	Benign	0.042	D;D
Sift4G	Benign	0.092	T;T
Polyphen		0.77	.;P
Vest4		0.79
MutPred		0.46		.;Loss of stability (P = 0.1383);
MVP		0.87
MPC		0.43
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.70
gMVP		0.89

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: chr12-331732;