chr8-17538903-T-G

Position:

• chr8-17538903-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000640220(SLC7A2):​c.-42T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC7A2 ENST00000640220 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.37

Genes affected

SLC7A2 (HGNC:11060): (solute carrier family 7 member 2) The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104699194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A2	NM_001370338.1	c.-22-4415T>G		intron_variant		ENST00000494857.6	NP_001357267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A2	ENST00000494857.6	c.-22-4415T>G		intron_variant		5	NM_001370338.1	ENSP00000419140.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Oct 12, 2024

The c.79T>G (p.C27G) alteration is located in exon 1 (coding exon 1) of the SLC7A2 gene. This alteration results from a T to G substitution at nucleotide position 79, causing the cysteine (C) at amino acid position 27 to be replaced by a glycine (G). 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
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.24
DANN	Benign	0.71
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.19	.;T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-0.81	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.050	N;N;N;.
REVEL	Benign	0.090
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		0.0	B;B;B;.
Vest4		0.18
MutPred		0.36		Gain of disorder (P = 0.0188);Gain of disorder (P = 0.0188);Gain of disorder (P = 0.0188);.;
MVP		0.40
MPC		0.022
ClinPred		0.053	T
GERP RS		-0.60
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-17396412;