12-46788532-T-A

Position:

• chr12-46788532-T-A

Variant summary

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

The NM_018018.5(SLC38A4):​c.206A>T​(p.Glu69Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC38A4 NM_018018.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.86

Genes affected

SLC38A4 (HGNC:14679): (solute carrier family 38 member 4) SLC38A4 is found predominantly in liver and transports both cationic and neutral amino acids. The transport of cationic amino acids by SLC38A4 is Na(+) and pH independent, while the transport of neutral amino acids is Na(+) and pH dependent (Hatanaka et al., 2001 [PubMed 11342143]).[supplied by OMIM, Mar 2008]

SLC38A4-AS1 (HGNC:):

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	Protein	UniProt
SLC38A4	NM_018018.5	c.206A>T	p.Glu69Val	missense_variant	4/17	ENST00000266579.9	NP_060488.2
SLC38A4	NM_001143824.2	c.206A>T	p.Glu69Val	missense_variant	3/16		NP_001137296.1
SLC38A4	XM_005268997.3	c.206A>T	p.Glu69Val	missense_variant	3/16		XP_005269054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC38A4	ENST00000266579.9	c.206A>T	p.Glu69Val	missense_variant	4/17	1	NM_018018.5	ENSP00000266579.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 16, 2024

The c.206A>T (p.E69V) alteration is located in exon 4 (coding exon 2) of the SLC38A4 gene. This alteration results from a A to T substitution at nucleotide position 206, causing the glutamic acid (E) at amino acid position 69 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T;T;T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	.;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.7	M;M;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Benign	0.086	T;T;.;.
Polyphen		0.99	D;D;.;.
Vest4		0.38
MutPred		0.45		Gain of catalytic residue at D68 (P = 5e-04);Gain of catalytic residue at D68 (P = 5e-04);Gain of catalytic residue at D68 (P = 5e-04);Gain of catalytic residue at D68 (P = 5e-04);
MVP		0.16
MPC		0.92
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.68

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: chr12-47182315;