chr12-222605-T-C

Position:

• chr12-222605-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016615.5(SLC6A13):​c.1442A>G​(p.Glu481Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC6A13 NM_016615.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A13	NM_016615.5	c.1442A>G	p.Glu481Gly	missense_variant	13/15	ENST00000343164.9	NP_057699.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A13	ENST00000343164.9	c.1442A>G	p.Glu481Gly	missense_variant	13/15	1	NM_016615.5	ENSP00000339260.4
SLC6A13	ENST00000445055.6	c.1166A>G	p.Glu389Gly	missense_variant	11/13	2		ENSP00000407104.2
SLC6A13	ENST00000539668.1	n.400A>G		non_coding_transcript_exon_variant	5/5	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

Oct 08, 2024

The c.1442A>G (p.E481G) alteration is located in exon 13 (coding exon 12) of the SLC6A13 gene. This alteration results from a A to G substitution at nucleotide position 1442, causing the glutamic acid (E) at amino acid position 481 to be replaced by a glycine (G). 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	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.039	D;T
Polyphen		0.23	.;B
Vest4		0.83
MutPred		0.59		.;Loss of stability (P = 0.0279);
MVP		0.75
MPC		0.44
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.75
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-331771;