16-87836706-C-T

Variant names:

• chr16-87836706-C-T
• rs12444670
• NM_003486.7:c.1141-59G>A

Variant summary

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

The NM_003486.7(SLC7A5):​c.1141-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,590,380 control chromosomes in the GnomAD database, including 51,572 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 0.26 (5521 hom., cov: 33)
  • Exomes 𝑓: 0.25 (46051 hom.)
• Consequence: SLC7A5 NM_003486.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 6 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: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics

SLC7A5-AS1 (HGNC:58301):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A5	NM_003486.7	MANE Select	c.1141-59G>A		intron	N/A	NP_003477.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A5	ENST00000261622.5	TSL:1 MANE Select	c.1141-59G>A		intron	N/A	ENSP00000261622.4	Q01650
	SLC7A5	ENST00000565644.6	TSL:1	c.343-59G>A		intron	N/A	ENSP00000454323.1	A0A0C4DGL4
	SLC7A5	ENST00000850914.1		c.1195-59G>A		intron	N/A	ENSP00000520997.1	A0ABJ7H8K0

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39824 AN: 152044 Hom.: 5504 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.246 AC: 353237 AN: 1438218 Hom.: 46051 Cov.: 28 AF XY: 0.251 AC XY: 180065 AN XY: 716452

African (AFR) AF: 0.309 AC: 10237 AN: 33172

American (AMR) AF: 0.255 AC: 11342 AN: 44466

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 6927 AN: 26040

East Asian (EAS) AF: 0.0449 AC: 1777 AN: 39546

South Asian (SAS) AF: 0.396 AC: 33959 AN: 85794

European-Finnish (FIN) AF: 0.236 AC: 10449 AN: 44190

Middle Eastern (MID) AF: 0.328 AC: 1882 AN: 5730

European-Non Finnish (NFE) AF: 0.239 AC: 262375 AN: 1099470

Other (OTH) AF: 0.239 AC: 14289 AN: 59810

GnomAD4 genome AF: 0.262 AC: 39875 AN: 152162 Hom.: 5521 Cov.: 33 AF XY: 0.262 AC XY: 19506 AN XY: 74388

African (AFR) AF: 0.303 AC: 12597 AN: 41516

American (AMR) AF: 0.249 AC: 3807 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3470

East Asian (EAS) AF: 0.0417 AC: 216 AN: 5186

South Asian (SAS) AF: 0.383 AC: 1847 AN: 4820

European-Finnish (FIN) AF: 0.235 AC: 2483 AN: 10584

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.251 AC: 17049 AN: 67978

Other (OTH) AF: 0.241 AC: 510 AN: 2116

Alfa AF: 0.276 Hom.: 748

Bravo AF: 0.261

Asia WGS AF: 0.193 AC: 673 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.19
DANN	Benign	0.60
PhyloP100		-0.29
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: rs12444670; hg19: chr16-87870312; COSMIC: COSV55367541; COSMIC: COSV55367541;