5-55633770-C-G

Variant names:

• chr5-55633770-C-G
• rs748225255
• NM_173514.4:c.1414G>C

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.1414G>C​(p.Gly472Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G472S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC38A9 NM_173514.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10
• Publications: 0 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, 0.871

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.1414G>C	p.Gly472Arg	missense	Exon 14 of 16	NP_775785.2	Q8NBW4-1
	SLC38A9	NM_001349382.1		c.1414G>C	p.Gly472Arg	missense	Exon 16 of 18	NP_001336311.1	Q8NBW4-1
	SLC38A9	NM_001349383.1		c.1414G>C	p.Gly472Arg	missense	Exon 16 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.1414G>C	p.Gly472Arg	missense	Exon 14 of 16	ENSP00000380074.2	Q8NBW4-1
	SLC38A9	ENST00000318672.7	TSL:2	c.1414G>C	p.Gly472Arg	missense	Exon 12 of 14	ENSP00000316596.3	Q8NBW4-1
	SLC38A9	ENST00000870431.1		c.1414G>C	p.Gly472Arg	missense	Exon 16 of 18	ENSP00000540490.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.059	T
Polyphen		0.97	D
Vest4		0.44
MutPred		0.79		Gain of methylation at G472 (P = 0.0405)
MVP		0.43
MPC		0.37
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.36
gMVP		0.86
Mutation Taster		=10/90	disease causing

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: rs748225255; hg19: chr5-54929598;