Variant 5-55645805-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173514.4(SLC38A9):c.1151A>G(p.Lys384Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,792 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC38A9
NM_173514.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.072436124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A9	NM_173514.4 linkuse as main transcript	c.1151A>G	p.Lys384Arg	missense_variant	12/16	ENST00000396865.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A9	ENST00000396865.7 linkuse as main transcript	c.1151A>G	p.Lys384Arg	missense_variant	12/16	1	NM_173514.4	P1	Q8NBW4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

247894

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000274

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453792

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723320

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.1151A>G (p.K384R) alteration is located in exon 12 (coding exon 10) of the SLC38A9 gene. This alteration results from a A to G substitution at nucleotide position 1151, causing the lysine (K) at amino acid position 384 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

Benign

0.064

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

T;T;T;.;.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

.;T;T;T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.072

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;N;.;.;.

MutationTaster

Benign

0.54

D;D;D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.77

N;N;N;N;N;N

REVEL

Benign

0.095

Sift

Benign

0.23

T;T;T;T;T;T

Sift4G

Benign

0.59

T;T;T;T;T;T

Polyphen

0.020

B;.;B;.;.;.

Vest4

0.19

MutPred

0.51

Loss of methylation at K384 (P = 0.0199);.;Loss of methylation at K384 (P = 0.0199);.;.;.;

MVP

0.082

MPC

0.19

ClinPred

0.065

GERP RS

4.5

Varity_R

0.074

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over