chr12-46204384-C-A

Position:

• chr12-46204384-C-A

Variant summary

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

The NM_030674.4(SLC38A1):​c.739G>T​(p.Val247Phe) 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. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC38A1 NM_030674.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.192

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A1	NM_030674.4	c.739G>T	p.Val247Phe	missense_variant	11/17	ENST00000398637.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A1	ENST00000398637.10	c.739G>T	p.Val247Phe	missense_variant	11/17	1	NM_030674.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jun 17, 2024

The c.739G>T (p.V247F) alteration is located in exon 11 (coding exon 9) of the SLC38A1 gene. This alteration results from a G to T substitution at nucleotide position 739, causing the valine (V) at amino acid position 247 to be replaced by a phenylalanine (F). 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	0.073
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T;T;T;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.37	.;.;.;T;.;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.063	T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.65	N;N;N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.79	N;N;N;N;N;.
REVEL	Benign	0.063
Sift	Benign	0.12	T;T;T;T;T;.
Sift4G	Benign	0.28	T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;B
Vest4		0.18
MutPred		0.53		Gain of catalytic residue at P244 (P = 0);Gain of catalytic residue at P244 (P = 0);Gain of catalytic residue at P244 (P = 0);Gain of catalytic residue at P244 (P = 0);Gain of catalytic residue at P244 (P = 0);Gain of catalytic residue at P244 (P = 0);
MVP		0.068
MPC		0.74
ClinPred		0.091	T
GERP RS		-0.85
Varity_R		0.054
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: -7

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: chr12-46598167;