rs3846502

Variant names:

• chr5-55668755-C-T
• rs3846502
• NM_173514.4:c.526+473G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173514.4(SLC38A9):​c.526+473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,054 control chromosomes in the GnomAD database, including 27,996 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 0.60 (27996 hom., cov: 33)
• Consequence: SLC38A9 NM_173514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 4 publications found

Genes affected

SLC38A9 (HGNC:26907): (solute carrier family 38 member 9) Enables L-arginine transmembrane transporter activity and L-leucine transmembrane transporter activity. Involved in amino acid transmembrane transport; cellular response to amino acid stimulus; and positive regulation of TOR signaling. Located in late endosome and lysosomal membrane. Is integral component of lysosomal membrane. Colocalizes with Ragulator complex. [provided by Alliance of Genome Resources, Apr 2022]

SLC38A9 Gene-Disease associations (from GenCC):

• lysosomal storage disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A9	NM_173514.4	MANE Select	c.526+473G>A		intron	N/A	NP_775785.2	Q8NBW4-1
	SLC38A9	NM_001349382.1		c.526+473G>A		intron	N/A	NP_001336311.1	Q8NBW4-1
	SLC38A9	NM_001349383.1		c.526+473G>A		intron	N/A	NP_001336312.1	Q8NBW4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A9	ENST00000396865.7	TSL:1 MANE Select	c.526+473G>A		intron	N/A	ENSP00000380074.2	Q8NBW4-1
	SLC38A9	ENST00000318672.7	TSL:2	c.526+473G>A		intron	N/A	ENSP00000316596.3	Q8NBW4-1
	SLC38A9	ENST00000870431.1		c.526+473G>A		intron	N/A	ENSP00000540490.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91233 AN: 151936 Hom.: 27987 Cov.: 33

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.600 AC: 91283 AN: 152054 Hom.: 27996 Cov.: 33 AF XY: 0.602 AC XY: 44755 AN XY: 74324

African (AFR) AF: 0.477 AC: 19769 AN: 41454

American (AMR) AF: 0.572 AC: 8739 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2183 AN: 3468

East Asian (EAS) AF: 0.470 AC: 2421 AN: 5156

South Asian (SAS) AF: 0.701 AC: 3380 AN: 4822

European-Finnish (FIN) AF: 0.696 AC: 7365 AN: 10576

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45292 AN: 67996

Other (OTH) AF: 0.606 AC: 1280 AN: 2112

Alfa AF: 0.629 Hom.: 5327

Bravo AF: 0.582

Asia WGS AF: 0.593 AC: 2065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.60
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3846502; hg19: chr5-54964583;