8-17543326-C-T

Variant names:

• chr8-17543326-C-T
• rs201409423
• NM_001370338.1:c.-14C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001370338.1(SLC7A2):​c.-14C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,602,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: SLC7A2 NM_001370338.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.305
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0924187).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370338.1. 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
	SLC7A2	NM_001370338.1	MANE Select	c.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 13	NP_001357267.1	P52569-1
	SLC7A2	NM_001370338.1	MANE Select	c.-14C>T		5_prime_UTR	Exon 3 of 13	NP_001357267.1	P52569-1
	SLC7A2	NM_001008539.4		c.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	NP_001008539.3	P52569-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A2	ENST00000494857.6	TSL:5 MANE Select	c.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 13	ENSP00000419140.2	P52569-1
	SLC7A2	ENST00000522656.5	TSL:1	c.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000430464.1	P52569-1
	SLC7A2	ENST00000640220.1	TSL:1	c.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000492016.2	P52569-1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000249 AC: 6 AN: 241142 AF XY: 0.0000384

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000221 AC: 32 AN: 1450136 Hom.: 0 Cov.: 32 AF XY: 0.0000194 AC XY: 14 AN XY: 720308

African (AFR) AF: 0.000332 AC: 11 AN: 33112

American (AMR) AF: 0.00 AC: 0 AN: 42996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 84216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.0000172 AC: 19 AN: 1106388

Other (OTH) AF: 0.0000334 AC: 2 AN: 59872

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

African (AFR) AF: 0.000169 AC: 7 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000529

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Uncertain	0.99
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.42	T
PhyloP100		0.30
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.11
Sift	Benign	0.12	T
Sift4G	Uncertain	0.011	D
Polyphen		0.0010	B
Vest4		0.33
MutPred		0.32		Loss of disorder (P = 0.0252)
MVP		0.65
MPC		0.020
ClinPred		0.056	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.17
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs201409423; hg19: chr8-17400835; COSMIC: COSV99134638;