12-226756-C-T

Variant names:

• chr12-226756-C-T
• rs555044
• NM_016615.5:c.936-242G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016615.5(SLC6A13):​c.936-242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000854 in 234,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000085 (0 hom.)
• Consequence: SLC6A13 NM_016615.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.936-242G>A		intron	N/A	NP_057699.2
	SLC6A13	NM_001190997.3		c.660-242G>A		intron	N/A	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.936-242G>A		intron	N/A	ENSP00000339260.4	Q9NSD5-1
	SLC6A13	ENST00000965063.1		c.936-242G>A		intron	N/A	ENSP00000635122.1
	SLC6A13	ENST00000445055.6	TSL:2	c.660-242G>A		intron	N/A	ENSP00000407104.2	Q9NSD5-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000854 AC: 2 AN: 234088 Hom.: 0 Cov.: 4 AF XY: 0.0000163 AC XY: 2 AN XY: 122524

African (AFR) AF: 0.00 AC: 0 AN: 6854

American (AMR) AF: 0.00 AC: 0 AN: 9072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6798

East Asian (EAS) AF: 0.00 AC: 0 AN: 13566

South Asian (SAS) AF: 0.0000351 AC: 1 AN: 28482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1004

European-Non Finnish (NFE) AF: 0.00000698 AC: 1 AN: 143280

Other (OTH) AF: 0.00 AC: 0 AN: 12962

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.97
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs555044; hg19: chr12-335922;