NM_173514.4:c.863C>G

Variant names:

• chr5-55652618-G-C
• NM_173514.4:c.863C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173514.4(SLC38A9):​c.863C>G​(p.Ser288Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC38A9 NM_173514.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.02
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25495404).

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.863C>G	p.Ser288Cys	missense	Exon 10 of 16	NP_775785.2	Q8NBW4-1
	SLC38A9	NM_001349382.1		c.863C>G	p.Ser288Cys	missense	Exon 12 of 18	NP_001336311.1	Q8NBW4-1
	SLC38A9	NM_001349383.1		c.863C>G	p.Ser288Cys	missense	Exon 12 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.863C>G	p.Ser288Cys	missense	Exon 10 of 16	ENSP00000380074.2	Q8NBW4-1
	SLC38A9	ENST00000318672.7	TSL:2	c.863C>G	p.Ser288Cys	missense	Exon 8 of 14	ENSP00000316596.3	Q8NBW4-1
	SLC38A9	ENST00000870431.1		c.863C>G	p.Ser288Cys	missense	Exon 12 of 18	ENSP00000540490.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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	Benign	0.21
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.081
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		9.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.20
Sift	Benign	0.063	T
Sift4G	Benign	0.13	T
Polyphen		0.028	B
Vest4		0.53
MutPred		0.66		Gain of methylation at K287 (P = 0.0166)
MVP		0.043
MPC		0.73
ClinPred		0.89	D
GERP RS		4.7
Varity_R		0.16
gMVP		0.75
Mutation Taster		=73/27	polymorphism

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

hg19: chr5-54948446;