chr16-68290429-G-T

Variant names:

• chr16-68290429-G-T
• rs1241334275
• NM_003983.6:c.683G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003983.6(SLC7A6):​c.683G>T​(p.Gly228Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. G228D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC7A6 NM_003983.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89
• Publications: 0 publications found

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]

SLC7A6OS Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• epilepsy, progressive myoclonic, 12

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003983.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A6	NM_003983.6	MANE Select	c.683G>T	p.Gly228Val	missense	Exon 5 of 11	NP_003974.3	Q92536
	SLC7A6	NM_001076785.3		c.683G>T	p.Gly228Val	missense	Exon 6 of 12	NP_001070253.1	Q92536

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A6	ENST00000219343.11	TSL:1 MANE Select	c.683G>T	p.Gly228Val	missense	Exon 5 of 11	ENSP00000219343.6	Q92536
	SLC7A6	ENST00000379152.7	TSL:1	n.650-780G>T		intron	N/A	ENSP00000368448.3	E7EPZ8
	SLC7A6	ENST00000566454.5	TSL:5	c.683G>T	p.Gly228Val	missense	Exon 6 of 12	ENSP00000455064.1	Q92536

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251488 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.9
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.026	D
Polyphen		0.98	D
Vest4		0.67
MutPred		0.54		Loss of disorder (P = 0.0122)
MVP		0.93
MPC		1.4
ClinPred		0.98	D
GERP RS		2.9
Varity_R		0.88
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

Other links and lift over

dbSNP: rs1241334275; hg19: chr16-68324332;