16-68302437-T-C

Variant summary

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

The NM_032178.3(SLC7A6OS):c.743A>G(p.Asn248Ser) 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: 32)
• Consequence: SLC7A6OS NM_032178.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A6OS	NM_032178.3	c.743A>G	p.Asn248Ser	missense_variant	4/5	ENST00000263997.11
SLC7A6OS	XM_011523372.4	c.*61A>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A6OS	ENST00000263997.11	c.743A>G	p.Asn248Ser	missense_variant	4/5	1	NM_032178.3	P1
SLC7A6OS	ENST00000561590.1	c.269A>G	p.Asn90Ser	missense_variant	2/2	2
SLC7A6OS	ENST00000561933.1	n.884A>G		non_coding_transcript_exon_variant	3/4	2
SLC7A6OS	ENST00000568315.1	c.*61A>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

Ambry Genetics

Jan 30, 2024

The c.743A>G (p.N248S) alteration is located in exon 4 (coding exon 4) of the SLC7A6OS gene. This alteration results from a A to G substitution at nucleotide position 743, causing the asparagine (N) at amino acid position 248 to be replaced by a serine (S). 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	0.43
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.35	T;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	3.3	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.5	D;.
REVEL	Benign	0.28
Sift	Uncertain	0.0070	D;.
Sift4G	Uncertain	0.054	T;D
Polyphen		1.0	D;.
Vest4		0.70
MutPred		0.39		Gain of phosphorylation at N248 (P = 0.0026);.;
MVP		0.53
MPC		1.3
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr16-68336340;