14-61037070-T-G

Variant names:

• chr14-61037070-T-G
• rs773589623
• NM_153811.3:c.494T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153811.3(SLC38A6):​c.494T>G​(p.Leu165Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,918 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L165P) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLC38A6 NM_153811.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26
• Publications: 0 publications found

Genes affected

SLC38A6 (HGNC:19863): (solute carrier family 38 member 6) Predicted to enable L-glutamine transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and glutamine transport. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307460 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153811.3. 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
	SLC38A6	NM_153811.3	MANE Select	c.494T>G	p.Leu165Arg	missense	Exon 7 of 16	NP_722518.2	Q8IZM9-1
	SLC38A6	NM_001172702.2		c.494T>G	p.Leu165Arg	missense	Exon 7 of 17	NP_001166173.1	Q8IZM9-2
	SLC38A6	NR_033344.2		n.836T>G		non_coding_transcript_exon	Exon 7 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A6	ENST00000267488.9	TSL:1 MANE Select	c.494T>G	p.Leu165Arg	missense	Exon 7 of 16	ENSP00000267488.4	Q8IZM9-1
	SLC38A6	ENST00000354886.6	TSL:1	c.494T>G	p.Leu165Arg	missense	Exon 7 of 17	ENSP00000346959.2	Q8IZM9-2
	SLC38A6	ENST00000451406.5	TSL:1	c.479T>G	p.Leu160Arg	missense	Exon 7 of 17	ENSP00000395851.1	A0A0C4DG39

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151918 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151918 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74194

African (AFR) AF: 0.0000242 AC: 1 AN: 41378

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.35
Sift	Benign	0.041	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.94
MVP		0.25
MPC		0.14
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.91
gMVP		0.85
Mutation Taster		=76/24	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: rs773589623; hg19: chr14-61503788;