12-46188978-C-T

Position:

• chr12-46188978-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030674.4(SLC38A1):​c.1456G>A​(p.Gly486Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC38A1 NM_030674.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

Genes affected

SLC38A1 (HGNC:13447): (solute carrier family 38 member 1) Amino acid transporters play essential roles in the uptake of nutrients, production of energy, chemical metabolism, detoxification, and neurotransmitter cycling. SLC38A1 is an important transporter of glutamine, an intermediate in the detoxification of ammonia and the production of urea. Glutamine serves as a precursor for the synaptic transmitter, glutamate (Gu et al., 2001 [PubMed 11325958]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1797424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A1	NM_030674.4	c.1456G>A	p.Gly486Ser	missense_variant	17/17	ENST00000398637.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A1	ENST00000398637.10	c.1456G>A	p.Gly486Ser	missense_variant	17/17	1	NM_030674.4	P1
SLC38A1	ENST00000439706.5	c.1456G>A	p.Gly486Ser	missense_variant	18/18	1		P1
SLC38A1	ENST00000546893.5	c.1456G>A	p.Gly486Ser	missense_variant	17/17	1		P1
SLC38A1	ENST00000549049.5	c.1456G>A	p.Gly486Ser	missense_variant	16/16	1		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.1456G>A (p.G486S) alteration is located in exon 17 (coding exon 15) of the SLC38A1 gene. This alteration results from a G to A substitution at nucleotide position 1456, causing the glycine (G) at amino acid position 486 to be replaced by a serine (S). 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	Benign	0.090
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;T;T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;L
MutationTaster	Benign	0.91	D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Benign	0.078
Sift	Uncertain	0.012	D;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		0.048	B;B;B;B
Vest4		0.34
MutPred		0.41		Gain of glycosylation at G486 (P = 0.0086);Gain of glycosylation at G486 (P = 0.0086);Gain of glycosylation at G486 (P = 0.0086);Gain of glycosylation at G486 (P = 0.0086);
MVP		0.082
MPC		1.5
ClinPred		0.84	D
GERP RS		4.5
Varity_R		0.070

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-46582761; COSMIC: COSV104705852;