NM_173514.4:c.-35+5381C>T

Variant names:

• chr5-55706071-G-A
• rs11958779
• NM_173514.4:c.-35+5381C>T

Variant summary

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

The NM_173514.4(SLC38A9):​c.-35+5381C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,610 control chromosomes in the GnomAD database, including 30,769 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 0.63 (30769 hom., cov: 31)
• Consequence: SLC38A9 NM_173514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 36 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A9	NM_173514.4	c.-35+5381C>T		intron_variant	Intron 2 of 15	ENST00000396865.7	NP_775785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A9	ENST00000396865.7	c.-35+5381C>T		intron_variant	Intron 2 of 15	1	NM_173514.4	ENSP00000380074.2

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95902 AN: 151492 Hom.: 30771 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.673

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.633 AC: 95938 AN: 151610 Hom.: 30769 Cov.: 31 AF XY: 0.634 AC XY: 46937 AN XY: 74050

African (AFR) AF: 0.540 AC: 22292 AN: 41290

American (AMR) AF: 0.589 AC: 8976 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2365 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2404 AN: 5150

South Asian (SAS) AF: 0.729 AC: 3518 AN: 4824

European-Finnish (FIN) AF: 0.705 AC: 7387 AN: 10484

Middle Eastern (MID) AF: 0.666 AC: 193 AN: 290

European-Non Finnish (NFE) AF: 0.689 AC: 46784 AN: 67854

Other (OTH) AF: 0.640 AC: 1344 AN: 2100

Alfa AF: 0.665 Hom.: 89405

Bravo AF: 0.617

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		-0.27
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: rs11958779; hg19: chr5-55001899;