16-68291607-C-T

Variant names:

• chr16-68291607-C-T
• NM_003983.6:c.968C>T

Variant summary

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

The NM_003983.6(SLC7A6):​c.968C>T​(p.Ala323Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC7A6 NM_003983.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

Genes affected

SLC7A6 (HGNC:11064): (solute carrier family 7 member 6) Enables basic amino acid transmembrane transporter activity. Involved in basic amino acid transmembrane transport and ornithine transport. Located in intracellular membrane-bounded organelle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000279649 (HGNC:):

SLC7A6OS (HGNC:25807): (solute carrier family 7 member 6 opposite strand) Predicted to be involved in developmental process. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in cytoplasm and nucleus. Implicated in progressive myoclonus epilepsy. [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
SLC7A6	NM_003983.6	c.968C>T	p.Ala323Val	missense_variant	Exon 7 of 11	ENST00000219343.11	NP_003974.3
SLC7A6	NM_001076785.3	c.968C>T	p.Ala323Val	missense_variant	Exon 8 of 12		NP_001070253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A6	ENST00000219343.11	c.968C>T	p.Ala323Val	missense_variant	Exon 7 of 11	1	NM_003983.6	ENSP00000219343.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.968C>T (p.A323V) alteration is located in exon 8 (coding exon 5) of the SLC7A6 gene. This alteration results from a C to T substitution at nucleotide position 968, causing the alanine (A) at amino acid position 323 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	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.5	N;N
REVEL	Pathogenic	0.71
Sift	Benign	0.23	T;T
Sift4G	Benign	0.25	T;T
Polyphen		0.93	P;P
Vest4		0.73
MutPred		0.46		Loss of glycosylation at S327 (P = 0.252);Loss of glycosylation at S327 (P = 0.252);
MVP		0.90
MPC		1.2
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.44
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-68325510;