NM_173514.4:c.1087A>T

Variant names:

• chr5-55645869-T-A
• rs187154786
• NM_173514.4:c.1087A>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_173514.4(SLC38A9):​c.1087A>T​(p.Thr363Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,610,042 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00054 (6 hom.)
• Consequence: SLC38A9 NM_173514.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.63
• Publications: 3 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013620943).
• BP6: Variant 5-55645869-T-A is Benign according to our data. Variant chr5-55645869-T-A is described in ClinVar as Benign. ClinVar VariationId is 731355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 Unknown gene

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.1087A>T	p.Thr363Ser	missense	Exon 12 of 16	NP_775785.2	Q8NBW4-1
	SLC38A9	NM_001349382.1		c.1087A>T	p.Thr363Ser	missense	Exon 14 of 18	NP_001336311.1	Q8NBW4-1
	SLC38A9	NM_001349383.1		c.1087A>T	p.Thr363Ser	missense	Exon 14 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.1087A>T	p.Thr363Ser	missense	Exon 12 of 16	ENSP00000380074.2	Q8NBW4-1
	SLC38A9	ENST00000318672.7	TSL:2	c.1087A>T	p.Thr363Ser	missense	Exon 10 of 14	ENSP00000316596.3	Q8NBW4-1
	SLC38A9	ENST00000870431.1		c.1087A>T	p.Thr363Ser	missense	Exon 14 of 18	ENSP00000540490.1

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 61 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00865

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00108 AC: 266 AN: 247372 AF XY: 0.000973

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0103

Gnomad FIN exome AF: 0.000419

Gnomad NFE exome AF: 0.000496

Gnomad OTH exome AF: 0.000991

GnomAD4 exome AF: 0.000539 AC: 786 AN: 1457776 Hom.: 6 Cov.: 29 AF XY: 0.000549 AC XY: 398 AN XY: 724986

African (AFR) AF: 0.0000602 AC: 2 AN: 33246

American (AMR) AF: 0.00 AC: 0 AN: 44010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.0119 AC: 472 AN: 39618

South Asian (SAS) AF: 0.000295 AC: 25 AN: 84876

European-Finnish (FIN) AF: 0.000563 AC: 30 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000191 AC: 212 AN: 1110622

Other (OTH) AF: 0.000746 AC: 45 AN: 60294

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00848 AC: 44 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68014

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000729 Hom.: 1

Bravo AF: 0.000476

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.00139 AC: 169

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.013
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Benign	0.40	T
Sift4G	Benign	0.42	T
Polyphen		0.053	B
Vest4		0.54
MutPred		0.61		Loss of sheet (P = 0.1158)
MVP		0.17
MPC		0.25
ClinPred		0.039	T
GERP RS		5.8
Varity_R		0.23
gMVP		0.59
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs187154786; hg19: chr5-54941697; COSMIC: COSV59423688; COSMIC: COSV59423688;