5-55626547-C-T

Variant names:

• chr5-55626547-C-T
• rs773927493
• NM_173514.4:c.1633G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_173514.4(SLC38A9):​c.1633G>A​(p.Val545Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,460,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: SLC38A9 NM_173514.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.952
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033024907).
• BP6: Variant 5-55626547-C-T is Benign according to our data. Variant chr5-55626547-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2229245.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1633G>A	p.Val545Ile	missense	Exon 16 of 16	NP_775785.2	Q8NBW4-1
	SLC38A9	NM_001349382.1		c.1633G>A	p.Val545Ile	missense	Exon 18 of 18	NP_001336311.1	Q8NBW4-1
	SLC38A9	NM_001349383.1		c.1633G>A	p.Val545Ile	missense	Exon 18 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.1633G>A	p.Val545Ile	missense	Exon 16 of 16	ENSP00000380074.2	Q8NBW4-1
	SLC38A9	ENST00000318672.7	TSL:2	c.1633G>A	p.Val545Ile	missense	Exon 14 of 14	ENSP00000316596.3	Q8NBW4-1
	SLC38A9	ENST00000870431.1		c.1633G>A	p.Val545Ile	missense	Exon 18 of 18	ENSP00000540490.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251036 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000130 AC: 19 AN: 1460196 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 726376

African (AFR) AF: 0.0000299 AC: 1 AN: 33426

American (AMR) AF: 0.0000896 AC: 4 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 85962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60306

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.063
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.033
DANN	Benign	0.52
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-0.95
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.072
Sift	Benign	0.94	T
Sift4G	Benign	0.59	T
Polyphen		0.0020	B
Vest4		0.017
MutPred		0.55		Loss of sheet (P = 0.1158)
MVP		0.082
MPC		0.19
ClinPred		0.012	T
GERP RS		-9.9
Varity_R		0.016
gMVP		0.21
Mutation Taster		=92/8	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

dbSNP: rs773927493; hg19: chr5-54922375;