NM_173514.4:c.1318T>C

Variant names:

• chr5-55633866-A-G
• rs149447829
• NM_173514.4:c.1318T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_173514.4(SLC38A9):​c.1318T>C​(p.Ser440Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00195 in 1,612,510 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (3 hom.)
• Consequence: SLC38A9 NM_173514.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.56
• Publications: 4 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026562274).
• BS2: High Homozygotes in GnomAdExome4 at 3 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.1318T>C	p.Ser440Pro	missense	Exon 14 of 16	NP_775785.2	Q8NBW4-1
	SLC38A9	NM_001349382.1		c.1318T>C	p.Ser440Pro	missense	Exon 16 of 18	NP_001336311.1	Q8NBW4-1
	SLC38A9	NM_001349383.1		c.1318T>C	p.Ser440Pro	missense	Exon 16 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.1318T>C	p.Ser440Pro	missense	Exon 14 of 16	ENSP00000380074.2	Q8NBW4-1
	SLC38A9	ENST00000318672.7	TSL:2	c.1318T>C	p.Ser440Pro	missense	Exon 12 of 14	ENSP00000316596.3	Q8NBW4-1
	SLC38A9	ENST00000870431.1		c.1318T>C	p.Ser440Pro	missense	Exon 16 of 18	ENSP00000540490.1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 193 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00220

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00122 AC: 303 AN: 248950 AF XY: 0.00115

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00202 AC: 2952 AN: 1460200 Hom.: 3 Cov.: 30 AF XY: 0.00199 AC XY: 1442 AN XY: 726288

African (AFR) AF: 0.000538 AC: 18 AN: 33436

American (AMR) AF: 0.00156 AC: 69 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000700 AC: 6 AN: 85756

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53408

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5728

European-Non Finnish (NFE) AF: 0.00249 AC: 2763 AN: 1111438

Other (OTH) AF: 0.00139 AC: 84 AN: 60332

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74478

African (AFR) AF: 0.000385 AC: 16 AN: 41568

American (AMR) AF: 0.00124 AC: 19 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00220 AC: 150 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00186 Hom.: 1

Bravo AF: 0.00141

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00174 AC: 15

ExAC AF: 0.00114 AC: 139

EpiCase AF: 0.00218

EpiControl AF: 0.00101

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Uncertain	0.40
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.18
Sift	Uncertain	0.023	D
Sift4G	Benign	0.12	T
Polyphen		0.78	P
Vest4		0.90
MVP		0.16
MPC		0.69
ClinPred		0.065	T
GERP RS		5.4
Varity_R		0.59
gMVP		0.92
Mutation Taster		=58/42	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: rs149447829; hg19: chr5-54929694; COSMIC: COSV105191914;