rs375396

Variant names:

• chr5-151287372-C-A
• rs375396
• NM_181774.4:c.582G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_181774.4(SLC36A3):​c.582G>T​(p.Leu194Leu) 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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC36A3	NM_181774.4	c.582G>T	p.Leu194Leu	synonymous_variant	Exon 6 of 10	ENST00000335230.8	NP_861439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC36A3	ENST00000335230.8	c.582G>T	p.Leu194Leu	synonymous_variant	Exon 6 of 10	1	NM_181774.4	ENSP00000334750.3
SLC36A3	ENST00000377713.3	c.705G>T	p.Leu235Leu	synonymous_variant	Exon 7 of 11	1		ENSP00000366942.3
SLC36A3	ENST00000423071.2	n.2482G>T		non_coding_transcript_exon_variant	Exon 5 of 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

GnomAD2 exomes AF: 0.219 AC: 54990 AN: 251438 AF XY: 0.220

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 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

African (AFR) AF: 0.192 AC: 6438 AN: 33480

American (AMR) AF: 0.167 AC: 7464 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6546 AN: 26136

East Asian (EAS) AF: 0.495 AC: 19668 AN: 39698

South Asian (SAS) AF: 0.249 AC: 21448 AN: 86254

European-Finnish (FIN) AF: 0.246 AC: 13127 AN: 53420

Middle Eastern (MID) AF: 0.200 AC: 1154 AN: 5768

European-Non Finnish (NFE) AF: 0.180 AC: 199898 AN: 1111988

Other (OTH) AF: 0.205 AC: 12362 AN: 60390

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

African (AFR) AF: 0.196 AC: 8125 AN: 41448

American (AMR) AF: 0.175 AC: 2671 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3466

East Asian (EAS) AF: 0.439 AC: 2267 AN: 5168

South Asian (SAS) AF: 0.252 AC: 1214 AN: 4812

European-Finnish (FIN) AF: 0.246 AC: 2603 AN: 10560

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12883 AN: 67978

Other (OTH) AF: 0.208 AC: 437 AN: 2104

Alfa AF: 0.181 Hom.: 2482

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
PhyloP100		-0.37
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs375396; hg19: chr5-150666933; COSMIC: COSV58856967;