14-61030469-T-C

Variant names:

• chr14-61030469-T-C
• rs781249288
• NM_153811.3:c.428T>C

Variant summary

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

The NM_153811.3(SLC38A6):​c.428T>C​(p.Ile143Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC38A6 NM_153811.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76

Genes affected

SLC38A6 (HGNC:19863): (solute carrier family 38 member 6) Predicted to enable L-glutamine transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and glutamine transport. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
SLC38A6	NM_153811.3	c.428T>C	p.Ile143Thr	missense_variant	Exon 6 of 16	ENST00000267488.9	NP_722518.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A6	ENST00000267488.9	c.428T>C	p.Ile143Thr	missense_variant	Exon 6 of 16	1	NM_153811.3	ENSP00000267488.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 247882 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134142

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.428T>C (p.I143T) alteration is located in exon 6 (coding exon 6) of the SLC38A6 gene. This alteration results from a T to C substitution at nucleotide position 428, causing the isoleucine (I) at amino acid position 143 to be replaced by a threonine (T). 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	0.68
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;T;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M;M;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.96	D;P;.;.
Vest4		0.89
MVP		0.29
MPC		0.056
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.72
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs781249288; hg19: chr14-61497187;