rs16943310

Positions:

• chr16-87832512-C-T

Variant summary

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

The NM_003486.7(SLC7A5):​c.*458G>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 0.0413 in 153,074 control chromosomes in the GnomAD database, including 414 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 0.042 (414 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (0 hom.)
• Consequence: SLC7A5 NM_003486.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

Genes affected

SLC7A5 (HGNC:11063): (solute carrier family 7 member 5) Enables L-leucine transmembrane transporter activity; L-tryptophan transmembrane transporter activity; and thyroid hormone transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. Is integral component of membrane. Part of amino acid transport complex; apical 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A5	NM_003486.7	c.*458G>A		3_prime_UTR_variant	10/10	ENST00000261622.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A5	ENST00000261622.5	c.*458G>A		3_prime_UTR_variant	10/10	1	NM_003486.7	P1
SLC7A5	ENST00000565644.5	c.*458G>A		3_prime_UTR_variant	10/10	1

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6294 AN: 151956 Hom.: 411 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.00300 AC: 3 AN: 1000 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 534

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0139

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0416 AC: 6321 AN: 152074 Hom.: 414 Cov.: 32 AF XY: 0.0406 AC XY: 3022 AN XY: 74366

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0509 Hom.: 66

Bravo AF: 0.0476

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.34
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs16943310; hg19: chr16-87866118;