rs748225255

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-55633770-C-G
• chr5-55633770-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A9	NM_173514.4	c.1414G>C	p.Gly472Arg	missense_variant	Exon 14 of 16	ENST00000396865.7	NP_775785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A9	ENST00000396865.7	c.1414G>C	p.Gly472Arg	missense_variant	Exon 14 of 16	1	NM_173514.4	ENSP00000380074.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;.;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	.;D;D;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.7	M;.;M;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0060	D;T;D;D;D;T
Sift4G	Uncertain	0.059	T;T;T;T;T;T
Polyphen		0.97	D;.;D;.;.;.
Vest4		0.44
MutPred		0.79		Gain of methylation at G472 (P = 0.0405);.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs748225255; hg19: chr5-54929598;