chr5-55635632-A-C

Position:

• chr5-55635632-A-C

Variant summary

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

The NM_173514.4(SLC38A9):​c.1193T>G​(p.Met398Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: SLC38A9 NM_173514.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.14

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A9	NM_173514.4	c.1193T>G	p.Met398Arg	missense_variant	13/16	ENST00000396865.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A9	ENST00000396865.7	c.1193T>G	p.Met398Arg	missense_variant	13/16	1	NM_173514.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461416 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727020

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000900

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 23, 2023

The c.1193T>G (p.M398R) alteration is located in exon 13 (coding exon 11) of the SLC38A9 gene. This alteration results from a T to G substitution at nucleotide position 1193, causing the methionine (M) at amino acid position 398 to be replaced by an arginine (R). 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	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Benign	0.87
DEOGEN2	Benign	0.069	T;T;T;.;.;T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;D;D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.72	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Benign	0.26	T;T;T;T;T;D
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		0.53	P;.;P;.;.;.
Vest4		0.72
MutPred		0.93		Gain of methylation at M398 (P = 0.0271);.;Gain of methylation at M398 (P = 0.0271);.;.;.;
MVP		0.15
MPC		0.45
ClinPred		0.39	T
GERP RS		5.9
Varity_R		0.56
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-54931460;