chr12-46766725-A-T

Position:

• chr12-46766725-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018018.5(SLC38A4):​c.1620T>A​(p.Asp540Glu) 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. 14/21 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: SLC38A4 NM_018018.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.315

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05969307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A4	NM_018018.5	c.1620T>A	p.Asp540Glu	missense_variant	17/17	ENST00000266579.9	NP_060488.2
SLC38A4	NM_001143824.2	c.1620T>A	p.Asp540Glu	missense_variant	16/16		NP_001137296.1
SLC38A4	XM_005268997.3	c.1620T>A	p.Asp540Glu	missense_variant	16/16		XP_005269054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC38A4	ENST00000266579.9	c.1620T>A	p.Asp540Glu	missense_variant	17/17	1	NM_018018.5	ENSP00000266579.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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.1620T>A (p.D540E) alteration is located in exon 17 (coding exon 15) of the SLC38A4 gene. This alteration results from a T to A substitution at nucleotide position 1620, causing the aspartic acid (D) at amino acid position 540 to be replaced by a glutamic acid (E). 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	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.24	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		0.0050	B;B
Vest4		0.069
MutPred		0.39		Gain of catalytic residue at P541 (P = 0);Gain of catalytic residue at P541 (P = 0);
MVP		0.043
MPC		0.24
ClinPred		0.64	D
GERP RS		-1.3
Varity_R		0.074
gMVP		0.53

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: chr12-47160508;