rs12879346

Positions:

• chr14-23183499-T-A
• chr14-23183499-T-C

Variant summary

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

The NM_012244.4(SLC7A8):​c.-585A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,022 control chromosomes in the GnomAD database, including 31,430 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 0.63 (31419 hom., cov: 30)
  • Exomes 𝑓: 0.68 (11 hom.)
• Consequence: SLC7A8 NM_012244.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

Genes affected

SLC7A8 (HGNC:11066): (solute carrier family 7 member 8) Enables several functions, including neutral amino acid transmembrane transporter activity; thyroid hormone transmembrane transporter activity; and toxin transmembrane transporter activity. Involved in L-alanine import across plasma membrane; L-leucine import across plasma membrane; and thyroid hormone transport. Located in plasma membrane. Part of basolateral plasma membrane and microvillus membrane. [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 (AMR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A8	NM_012244.4	c.-585A>T		5_prime_UTR_variant	1/11	ENST00000316902.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A8	ENST00000316902.12	c.-585A>T		5_prime_UTR_variant	1/11	1	NM_012244.4	P1
SLC7A8	ENST00000469263.5	c.-585A>T		5_prime_UTR_variant	1/6	1
SLC7A8	ENST00000524758.1	c.-78A>T		5_prime_UTR_variant	1/3	4
SLC7A8	ENST00000525062.1	c.-273A>T		5_prime_UTR_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95909 AN: 151860 Hom.: 31397 Cov.: 30

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.652

GnomAD4 exome AF: 0.682 AC: 30 AN: 44 Hom.: 11 Cov.: 0 AF XY: 0.633 AC XY: 19 AN XY: 30

Gnomad4 EAS exome AF: 0.750

Gnomad4 NFE exome AF: 0.719

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.631 AC: 95967 AN: 151978 Hom.: 31419 Cov.: 30 AF XY: 0.629 AC XY: 46734 AN XY: 74296

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.647

Alfa AF: 0.692 Hom.: 20322

Bravo AF: 0.627

Asia WGS AF: 0.497 AC: 1727 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	7.6
DANN	Benign	0.65

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: rs12879346; hg19: chr14-23652708;