rs16884434

Variant names:

• chr5-55683170-A-G
• rs16884434
• NM_173514.4:c.114-10475T>C

Variant summary

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

The NM_173514.4(SLC38A9):​c.114-10475T>C 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 152,040 control chromosomes in the GnomAD database, including 27,948 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 (27948 hom., cov: 31)
• Consequence: SLC38A9 NM_173514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.679 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.114-10475T>C		intron	N/A	NP_775785.2	Q8NBW4-1
	SLC38A9	NM_001349382.1		c.114-10475T>C		intron	N/A	NP_001336311.1	Q8NBW4-1
	SLC38A9	NM_001349383.1		c.114-10475T>C		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.114-10475T>C		intron	N/A	ENSP00000380074.2	Q8NBW4-1
	SLC38A9	ENST00000318672.7	TSL:2	c.114-10475T>C		intron	N/A	ENSP00000316596.3	Q8NBW4-1
	SLC38A9	ENST00000870431.1		c.114-10475T>C		intron	N/A	ENSP00000540490.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91151 AN: 151922 Hom.: 27939 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.600 AC: 91203 AN: 152040 Hom.: 27948 Cov.: 31 AF XY: 0.602 AC XY: 44714 AN XY: 74310

African (AFR) AF: 0.479 AC: 19842 AN: 41456

American (AMR) AF: 0.571 AC: 8731 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2147 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2416 AN: 5168

South Asian (SAS) AF: 0.699 AC: 3360 AN: 4810

European-Finnish (FIN) AF: 0.697 AC: 7353 AN: 10554

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45214 AN: 67988

Other (OTH) AF: 0.609 AC: 1285 AN: 2110

Alfa AF: 0.629 Hom.: 5309

Bravo AF: 0.582

Asia WGS AF: 0.591 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		0.86
Mutation Taster		=100/0	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: rs16884434; hg19: chr5-54978998; COSMIC: COSV107388772;