rs375396

Positions:

• chr5-151287372-C-A
• chr5-151287372-C-G
• chr5-151287372-C-T

Variant summary

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

The NM_181774.4(SLC36A3):​c.582G>T​(p.Leu194=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,876 control chromosomes in the GnomAD database, including 34,903 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 0.21 (3492 hom., cov: 31)
  • Exomes 𝑓: 0.20 (31411 hom.)
• Consequence: SLC36A3 NM_181774.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

Genes affected

SLC36A3 (HGNC:19659): (solute carrier family 36 member 3) Predicted to enable amino acid transmembrane transporter activity. Predicted to be involved in amino acid transport and proton transmembrane transport. Predicted to be integral component of membrane. [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=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.374 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC36A3	NM_181774.4	c.582G>T	p.Leu194=	synonymous_variant	6/10	ENST00000335230.8	NP_861439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC36A3	ENST00000335230.8	c.582G>T	p.Leu194=	synonymous_variant	6/10	1	NM_181774.4	ENSP00000334750	P1
SLC36A3	ENST00000377713.3	c.705G>T	p.Leu235=	synonymous_variant	7/11	1		ENSP00000366942
SLC36A3	ENST00000423071.2	n.2482G>T		non_coding_transcript_exon_variant	5/9	2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31358 AN: 151900 Hom.: 3487 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.205

GnomAD3 exomes AF: 0.219 AC: 54990 AN: 251438 Hom.: 6729 AF XY: 0.220 AC XY: 29852 AN XY: 135894

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.429

Gnomad SAS exome AF: 0.254

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.197 AC: 288105 AN: 1461858 Hom.: 31411 Cov.: 51 AF XY: 0.199 AC XY: 144744 AN XY: 727232

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.206 AC: 31387 AN: 152018 Hom.: 3492 Cov.: 31 AF XY: 0.209 AC XY: 15526 AN XY: 74316

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.208

Alfa AF: 0.180 Hom.: 2300

Bravo AF: 0.200

Asia WGS AF: 0.351 AC: 1222 AN: 3478

EpiCase AF: 0.183

EpiControl AF: 0.186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.9
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375396; hg19: chr5-150666933; COSMIC: COSV58856967;