12-223196-C-A

Variant names:

• chr12-223196-C-A
• NM_016615.5:c.1350G>T
• SLC6A13 p.Ala450Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016615.5(SLC6A13):​c.1350G>T​(p.Ala450Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A450A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A13 NM_016615.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-1.9 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016615.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A13	NM_016615.5	MANE Select	c.1350G>T	p.Ala450Ala	synonymous	Exon 12 of 15	NP_057699.2
	SLC6A13	NM_001190997.3		c.1074G>T	p.Ala358Ala	synonymous	Exon 10 of 13	NP_001177926.1	Q9NSD5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A13	ENST00000343164.9	TSL:1 MANE Select	c.1350G>T	p.Ala450Ala	synonymous	Exon 12 of 15	ENSP00000339260.4	Q9NSD5-1
	SLC6A13	ENST00000965063.1		c.1212G>T	p.Ala404Ala	synonymous	Exon 11 of 14	ENSP00000635122.1
	SLC6A13	ENST00000445055.6	TSL:2	c.1074G>T	p.Ala358Ala	synonymous	Exon 10 of 13	ENSP00000407104.2	Q9NSD5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.091
DANN	Benign	0.60
PhyloP100		-1.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-332362;