14-61030445-C-T

Variant names:

• chr14-61030445-C-T
• rs750915264
• NM_153811.3:c.404C>T

Variant summary

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

The NM_153811.3(SLC38A6):​c.404C>T​(p.Ala135Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000138 in 1,447,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A135G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC38A6 NM_153811.3 missense, splice_region
• Scores: Splicing: ADA: 0.9772
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69

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.404C>T	p.Ala135Val	missense_variant, splice_region_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.404C>T	p.Ala135Val	missense_variant, splice_region_variant	Exon 6 of 16	1	NM_153811.3	ENSP00000267488.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447152 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 2 AN XY: 720140

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	.;T;T;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.0	M;M;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Uncertain	0.33
Sift	Benign	0.057	T;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.81
MVP		0.34
MPC		0.13
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.89
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.83
SpliceAI score (max)		0.050		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: rs750915264; hg19: chr14-61497163;