chr5-55649258-C-T

Variant names:

• chr5-55649258-C-T
• rs963747667
• NM_173514.4:c.1009G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173514.4(SLC38A9):​c.1009G>A​(p.Gly337Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC38A9 NM_173514.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.05
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

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.1009G>A	p.Gly337Arg	missense	Exon 11 of 16	NP_775785.2	Q8NBW4-1
	SLC38A9	NM_001349382.1		c.1009G>A	p.Gly337Arg	missense	Exon 13 of 18	NP_001336311.1	Q8NBW4-1
	SLC38A9	NM_001349383.1		c.1009G>A	p.Gly337Arg	missense	Exon 13 of 18	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.1009G>A	p.Gly337Arg	missense	Exon 11 of 16	ENSP00000380074.2	Q8NBW4-1
	SLC38A9	ENST00000318672.7	TSL:2	c.1009G>A	p.Gly337Arg	missense	Exon 9 of 14	ENSP00000316596.3	Q8NBW4-1
	SLC38A9	ENST00000870431.1		c.1009G>A	p.Gly337Arg	missense	Exon 13 of 18	ENSP00000540490.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
PhyloP100		7.0
Varity_R		0.93
gMVP		0.93
Mutation Taster		=13/87	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs963747667; hg19: chr5-54945086;