chr16-87831663-C-CGGG

Variant names:

• chr16-87831663-C-CGGG
• rs5818648
• NM_003486.7:c.*1304_*1306dupCCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003486.7(SLC7A5):​c.*1304_*1306dupCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (22958 hom., cov: 0)
  • Exomes 𝑓: 0.48 (6 hom.)
• Consequence: SLC7A5 NM_003486.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 3 publications found

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]

SLC7A5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000260466 (HGNC:58301):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A5	NM_003486.7	c.*1304_*1306dupCCC		3_prime_UTR_variant	Exon 10 of 10	ENST00000261622.5	NP_003477.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A5	ENST00000261622.5	c.*1304_*1306dupCCC		3_prime_UTR_variant	Exon 10 of 10	1	NM_003486.7	ENSP00000261622.4
SLC7A5	ENST00000565644.6	c.*1304_*1306dupCCC		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000454323.1
SLC7A5	ENST00000850914.1	c.*1304_*1306dupCCC		3_prime_UTR_variant	Exon 10 of 10			ENSP00000520997.1
ENSG00000260466	ENST00000825115.1	n.248-5748_248-5746dupGGG		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80479 AN: 151680 Hom.: 22915 Cov.: 0

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.477 AC: 21 AN: 44 Hom.: 6 Cov.: 0 AF XY: 0.545 AC XY: 12 AN XY: 22

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.409 AC: 9 AN: 22

Other (OTH) AF: 0.500 AC: 5 AN: 10

GnomAD4 genome AF: 0.531 AC: 80576 AN: 151798 Hom.: 22958 Cov.: 0 AF XY: 0.538 AC XY: 39908 AN XY: 74190

African (AFR) AF: 0.702 AC: 29052 AN: 41392

American (AMR) AF: 0.606 AC: 9254 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1400 AN: 3468

East Asian (EAS) AF: 0.833 AC: 4271 AN: 5128

South Asian (SAS) AF: 0.584 AC: 2807 AN: 4808

European-Finnish (FIN) AF: 0.427 AC: 4496 AN: 10536

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27669 AN: 67894

Other (OTH) AF: 0.493 AC: 1041 AN: 2112

Alfa AF: 0.265 Hom.: 459

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5818648; hg19: chr16-87865269; COSMIC: COSV55362721; COSMIC: COSV55362721;