12-223196-C-T

Position:

• chr12-223196-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016615.5(SLC6A13):​c.1350G>A​(p.Ala450=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,611,478 control chromosomes in the GnomAD database, including 31,412 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 0.20 (3120 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28292 hom.)
• Consequence: SLC6A13 NM_016615.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-1.9 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A13	NM_016615.5	c.1350G>A	p.Ala450=	synonymous_variant	12/15	ENST00000343164.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A13	ENST00000343164.9	c.1350G>A	p.Ala450=	synonymous_variant	12/15	1	NM_016615.5	P1
SLC6A13	ENST00000445055.6	c.1074G>A	p.Ala358=	synonymous_variant	10/13	2
SLC6A13	ENST00000539668.1	n.308G>A		non_coding_transcript_exon_variant	4/5	5
SLC6A13	ENST00000542379.1	n.258G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30372 AN: 151896 Hom.: 3115 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.194

GnomAD3 exomes AF: 0.185 AC: 46512 AN: 251030 Hom.: 4633 AF XY: 0.188 AC XY: 25518 AN XY: 135678

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.181

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.193 AC: 282057 AN: 1459466 Hom.: 28292 Cov.: 31 AF XY: 0.193 AC XY: 140195 AN XY: 726170

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.200 AC: 30405 AN: 152012 Hom.: 3120 Cov.: 32 AF XY: 0.199 AC XY: 14809 AN XY: 74290

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.193

Alfa AF: 0.190 Hom.: 3997

Bravo AF: 0.200

Asia WGS AF: 0.153 AC: 531 AN: 3478

EpiCase AF: 0.192

EpiControl AF: 0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.49
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs2289954; hg19: chr12-332362; COSMIC: COSV58255963; COSMIC: COSV58255963;