12-226756-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016615.5(SLC6A13):​c.936-242G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 385,580 control chromosomes in the GnomAD database, including 16,326 homozygotes. 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: 𝑓 0.31 (7652 hom., cov: 33)
  • Exomes 𝑓: 0.26 (8674 hom.)
• Consequence: SLC6A13 NM_016615.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A13	NM_016615.5	c.936-242G>T		intron_variant	Intron 8 of 14	ENST00000343164.9	NP_057699.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A13	ENST00000343164.9	c.936-242G>T		intron_variant	Intron 8 of 14	1	NM_016615.5	ENSP00000339260.4

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46432 AN: 151966 Hom.: 7637 Cov.: 33

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.259 AC: 60496 AN: 233494 Hom.: 8674 Cov.: 4 AF XY: 0.248 AC XY: 30368 AN XY: 122220

African (AFR) AF: 0.426 AC: 2911 AN: 6836

American (AMR) AF: 0.210 AC: 1898 AN: 9056

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 1884 AN: 6782

East Asian (EAS) AF: 0.374 AC: 5050 AN: 13510

South Asian (SAS) AF: 0.119 AC: 3384 AN: 28448

European-Finnish (FIN) AF: 0.314 AC: 3773 AN: 12032

Middle Eastern (MID) AF: 0.270 AC: 271 AN: 1002

European-Non Finnish (NFE) AF: 0.265 AC: 37844 AN: 142898

Other (OTH) AF: 0.269 AC: 3481 AN: 12930

GnomAD4 genome AF: 0.306 AC: 46483 AN: 152086 Hom.: 7652 Cov.: 33 AF XY: 0.304 AC XY: 22574 AN XY: 74354

African (AFR) AF: 0.427 AC: 17704 AN: 41474

American (AMR) AF: 0.257 AC: 3934 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3468

East Asian (EAS) AF: 0.354 AC: 1826 AN: 5156

South Asian (SAS) AF: 0.107 AC: 514 AN: 4818

European-Finnish (FIN) AF: 0.293 AC: 3102 AN: 10588

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17479 AN: 67966

Other (OTH) AF: 0.306 AC: 646 AN: 2114

Alfa AF: 0.271 Hom.: 18297

Bravo AF: 0.310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.83
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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;