12-226412-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_016615.5(SLC6A13):c.1038C>G(p.Pro346=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000991 in 1,614,046 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00081 (9 hom.)
• Consequence: SLC6A13 NM_016615.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 12-226412-G-C is Benign according to our data. Variant chr12-226412-G-C is described in ClinVar as [Benign]. Clinvar id is 731113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.27 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A13	NM_016615.5	c.1038C>G	p.Pro346=	synonymous_variant	9/15	ENST00000343164.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A13	ENST00000343164.9	c.1038C>G	p.Pro346=	synonymous_variant	9/15	1	NM_016615.5	P1

Frequencies

GnomAD3 genomes AF: 0.00278 AC: 423 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00690

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00137 AC: 344 AN: 251414 Hom.: 2 AF XY: 0.00114 AC XY: 155 AN XY: 135892

Gnomad AFR exome AF: 0.00683

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00754

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000536

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.000806 AC: 1178 AN: 1461728 Hom.: 9 Cov.: 31 AF XY: 0.000776 AC XY: 564 AN XY: 727160

Gnomad4 AFR exome AF: 0.00929

Gnomad4 AMR exome AF: 0.00284

Gnomad4 ASJ exome AF: 0.00681

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000373

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00277 AC: 422 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.00290 AC XY: 216 AN XY: 74488

Gnomad4 AFR AF: 0.00686

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00241 Hom.: 0

Bravo AF: 0.00339

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	7.5
Dann	Benign	0.74

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: rs76709380; hg19: chr12-335578;