5-55635612-G-C

Variant names:

• chr5-55635612-G-C
• NM_173514.4:c.1213C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173514.4(SLC38A9):​c.1213C>G​(p.Leu405Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC38A9 NM_173514.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20687765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A9	NM_173514.4	c.1213C>G	p.Leu405Val	missense_variant	Exon 13 of 16	ENST00000396865.7	NP_775785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A9	ENST00000396865.7	c.1213C>G	p.Leu405Val	missense_variant	Exon 13 of 16	1	NM_173514.4	ENSP00000380074.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1213C>G (p.L405V) alteration is located in exon 13 (coding exon 11) of the SLC38A9 gene. This alteration results from a C to G substitution at nucleotide position 1213, causing the leucine (L) at amino acid position 405 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.52
DEOGEN2	Benign	0.012	T;T;T;.;.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	.;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.;M;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.89	N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.39	T;T;T;T;T;T
Sift4G	Benign	0.57	T;T;T;T;T;T
Polyphen		0.32	B;.;B;.;.;.
Vest4		0.46
MutPred		0.53		Gain of loop (P = 0.0502);.;Gain of loop (P = 0.0502);.;.;.;
MVP		0.17
MPC		0.27
ClinPred		0.48	T
GERP RS		3.3
Varity_R		0.068
gMVP		0.50

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-54931440;