16-58671096-C-A

Variant names:

• chr16-58671096-C-A
• NM_018231.3:c.1180G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018231.3(SLC38A7):​c.1180G>T​(p.Val394Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC38A7 NM_018231.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

Genes affected

SLC38A7 (HGNC:25582): (solute carrier family 38 member 7) Predicted to enable L-amino acid transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and sodium ion transport. Predicted to be located in axon and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.752

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A7	NM_018231.3	c.1180G>T	p.Val394Leu	missense_variant	Exon 10 of 12	ENST00000219320.9	NP_060701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A7	ENST00000219320.9	c.1180G>T	p.Val394Leu	missense_variant	Exon 10 of 12	1	NM_018231.3	ENSP00000219320.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1180G>T (p.V394L) alteration is located in exon 10 (coding exon 8) of the SLC38A7 gene. This alteration results from a G to T substitution at nucleotide position 1180, causing the valine (V) at amino acid position 394 to be replaced by a leucine (L). 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.8	M;M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.88
MutPred		0.54		Loss of methylation at K393 (P = 0.0354);Loss of methylation at K393 (P = 0.0354);.;
MVP		0.64
MPC		0.81
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.50
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-58705000;