5-55690947-T-C

Variant names:

• chr5-55690947-T-C
• rs6897117
• NM_173514.4:c.113+6899A>G

Variant summary

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

The NM_173514.4(SLC38A9):​c.113+6899A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,048 control chromosomes in the GnomAD database, including 38,545 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 0.71 (38545 hom., cov: 32)
• Consequence: SLC38A9 NM_173514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A9	NM_173514.4	c.113+6899A>G		intron_variant	Intron 3 of 15	ENST00000396865.7	NP_775785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A9	ENST00000396865.7	c.113+6899A>G		intron_variant	Intron 3 of 15	1	NM_173514.4	ENSP00000380074.2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108078 AN: 151930 Hom.: 38521 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.711 AC: 108156 AN: 152048 Hom.: 38545 Cov.: 32 AF XY: 0.715 AC XY: 53183 AN XY: 74348

African (AFR) AF: 0.716 AC: 29670 AN: 41442

American (AMR) AF: 0.713 AC: 10893 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2414 AN: 3472

East Asian (EAS) AF: 0.715 AC: 3698 AN: 5172

South Asian (SAS) AF: 0.821 AC: 3957 AN: 4818

European-Finnish (FIN) AF: 0.725 AC: 7671 AN: 10584

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.699 AC: 47496 AN: 67968

Other (OTH) AF: 0.703 AC: 1484 AN: 2110

Alfa AF: 0.714 Hom.: 7277

Bravo AF: 0.709

Asia WGS AF: 0.778 AC: 2708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		-0.064
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: rs6897117; hg19: chr5-54986775; COSMIC: COSV59424559; COSMIC: COSV59424559;