rs1127773

Positions:

• chr16-68298844-G-A
• chr16-68298844-G-C
• chr16-68298844-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003983.6(SLC7A6):​c.*1516G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,432 control chromosomes in the GnomAD database, including 20,187 homozygotes. 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: 𝑓 0.50 (20141 hom., cov: 32)
  • Exomes 𝑓: 0.52 (46 hom.)
• Consequence: SLC7A6 NM_003983.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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]

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A6	NM_003983.6	c.*1516G>A		3_prime_UTR_variant	11/11	ENST00000219343.11
SLC7A6OS	NM_032178.3	c.*2431C>T		3_prime_UTR_variant	5/5	ENST00000263997.11
SLC7A6	NM_001076785.3	c.*1516G>A		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A6	ENST00000219343.11	c.*1516G>A		3_prime_UTR_variant	11/11	1	NM_003983.6	P1
SLC7A6OS	ENST00000263997.11	c.*2431C>T		3_prime_UTR_variant	5/5	1	NM_032178.3	P1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76414 AN: 151912 Hom.: 20131 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.520 AC: 209 AN: 402 Hom.: 46 Cov.: 0 AF XY: 0.523 AC XY: 137 AN XY: 262

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.503 AC: 76458 AN: 152030 Hom.: 20141 Cov.: 32 AF XY: 0.501 AC XY: 37192 AN XY: 74296

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.509

Alfa AF: 0.533 Hom.: 28881

Bravo AF: 0.511

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.3
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs1127773; hg19: chr16-68332747; COSMIC: COSV50450879; COSMIC: COSV50450879;