16-68302421-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_032178.3(SLC7A6OS):c.759C>G(p.Tyr253Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC7A6OS NM_032178.3 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.748

Genes affected

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_032178.3 Downstream stopcodon found after 7 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A6OS	NM_032178.3	c.759C>G	p.Tyr253Ter	stop_gained	4/5	ENST00000263997.11
SLC7A6OS	XM_011523372.4	c.*77C>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A6OS	ENST00000263997.11	c.759C>G	p.Tyr253Ter	stop_gained	4/5	1	NM_032178.3	P1
SLC7A6OS	ENST00000561590.1	c.285C>G	p.Tyr95Ter	stop_gained	2/2	2
SLC7A6OS	ENST00000561933.1	n.900C>G		non_coding_transcript_exon_variant	3/4	2
SLC7A6OS	ENST00000568315.1	c.*77C>G		3_prime_UTR_variant, NMD_transcript_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Sep 01, 2023

Variant summary: SLC7A6OS c.759C>G (p.Tyr253X) results in a premature termination codon and is predicted to cause a truncation of the encoded protein. Although the variant is not predicted to cause absence of the protein through nonsense mediated decay, the variant disrupts the last 57 amino acids in the protein sequence. The molecular mechanism of disease attributed to SLC7A6OS is currently unknown. The variant was absent in 251472 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.759C>G in individuals affected with Epilepsy, Progressive Myoclonic, 12 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
Cadd	Pathogenic	35
Dann	Uncertain	1.0
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.86	D
MutationTaster	Benign	1.0	D
Vest4		0.27
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr16-68336324;