12-224059-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016615.5(SLC6A13):c.1244G>A(p.Arg415Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00109 in 1,614,108 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00060 (7 hom.)
• Consequence: SLC6A13 NM_016615.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.01

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018333673).
• BP6: Variant 12-224059-C-T is Benign according to our data. Variant chr12-224059-C-T is described in ClinVar as [Benign]. Clinvar id is 787549.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-224059-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00579 (882/152262) while in subpopulation AFR AF= 0.0194 (807/41548). AF 95% confidence interval is 0.0183. There are 13 homozygotes in gnomad4. There are 453 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A13	NM_016615.5	c.1244G>A	p.Arg415Gln	missense_variant	11/15	ENST00000343164.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A13	ENST00000343164.9	c.1244G>A	p.Arg415Gln	missense_variant	11/15	1	NM_016615.5	P1

Frequencies

GnomAD3 genomes AF: 0.00578 AC: 879 AN: 152144 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00161 AC: 404 AN: 251444 Hom.: 5 AF XY: 0.00114 AC XY: 155 AN XY: 135890

Gnomad AFR exome AF: 0.0210

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000791

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000603 AC: 881 AN: 1461846 Hom.: 7 Cov.: 32 AF XY: 0.000516 AC XY: 375 AN XY: 727230

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000728

Gnomad4 OTH exome AF: 0.00124

GnomAD4 genome AF: 0.00579 AC: 882 AN: 152262 Hom.: 13 Cov.: 33 AF XY: 0.00609 AC XY: 453 AN XY: 74442

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00115 Hom.: 0

Bravo AF: 0.00671

ESP6500AA AF: 0.0213 AC: 94

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00200 AC: 243

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.18
Cadd	Uncertain	25
Dann	Pathogenic	1.0
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
MetaRNN	Benign	0.018	T;T
MetaSVM	Uncertain	-0.0052	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.51
Sift	Benign	0.081	T;T
Sift4G	Uncertain	0.051	T;T
Polyphen		0.95	.;P
Vest4		0.51
MVP		0.71
MPC		0.11
ClinPred		0.035	T
GERP RS		5.5
Varity_R		0.69
gMVP		0.55

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: rs145646067; hg19: chr12-333225;