16-87838108-T-G

Variant names:

• chr16-87838108-T-G
• rs2287121
• NM_003486.7:c.1044-167A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003486.7(SLC7A5):​c.1044-167A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,024 control chromosomes in the GnomAD database, including 34,756 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 0.67 (34756 hom., cov: 33)
• Consequence: SLC7A5 NM_003486.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 7 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003486.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A5	NM_003486.7	MANE Select	c.1044-167A>C		intron	N/A	NP_003477.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A5	ENST00000261622.5	TSL:1 MANE Select	c.1044-167A>C		intron	N/A	ENSP00000261622.4
	SLC7A5	ENST00000565644.6	TSL:1	c.246-167A>C		intron	N/A	ENSP00000454323.1
	SLC7A5	ENST00000850914.1		c.1098-167A>C		intron	N/A	ENSP00000520997.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101451 AN: 151906 Hom.: 34704 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.627

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.668 AC: 101556 AN: 152024 Hom.: 34756 Cov.: 33 AF XY: 0.678 AC XY: 50395 AN XY: 74320

African (AFR) AF: 0.780 AC: 32377 AN: 41506

American (AMR) AF: 0.728 AC: 11120 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1763 AN: 3462

East Asian (EAS) AF: 0.846 AC: 4368 AN: 5162

South Asian (SAS) AF: 0.816 AC: 3934 AN: 4820

European-Finnish (FIN) AF: 0.653 AC: 6886 AN: 10552

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39037 AN: 67928

Other (OTH) AF: 0.625 AC: 1318 AN: 2110

Alfa AF: 0.603 Hom.: 42515

Bravo AF: 0.674

Asia WGS AF: 0.824 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.47
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2287121; hg19: chr16-87871714;