NM_003486.7:c.940-421T>C

Variant names:

• chr16-87839238-A-G
• rs4843713
• NM_003486.7:c.940-421T>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.940-421T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,114 control chromosomes in the GnomAD database, including 39,578 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 0.71 (39578 hom., cov: 33)
• Consequence: SLC7A5 NM_003486.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 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.940-421T>C		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.940-421T>C		intron	N/A	ENSP00000261622.4	Q01650
	SLC7A5	ENST00000565644.6	TSL:1	c.142-421T>C		intron	N/A	ENSP00000454323.1	A0A0C4DGL4
	SLC7A5	ENST00000850914.1		c.994-421T>C		intron	N/A	ENSP00000520997.1	A0ABJ7H8K0

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108118 AN: 151996 Hom.: 39520 Cov.: 33

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.712 AC: 108234 AN: 152114 Hom.: 39578 Cov.: 33 AF XY: 0.723 AC XY: 53736 AN XY: 74374

African (AFR) AF: 0.855 AC: 35495 AN: 41536

American (AMR) AF: 0.767 AC: 11721 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1871 AN: 3470

East Asian (EAS) AF: 0.847 AC: 4353 AN: 5140

South Asian (SAS) AF: 0.852 AC: 4120 AN: 4834

European-Finnish (FIN) AF: 0.683 AC: 7239 AN: 10600

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41146 AN: 67932

Other (OTH) AF: 0.683 AC: 1439 AN: 2108

Alfa AF: 0.600 Hom.: 2003

Bravo AF: 0.719

Asia WGS AF: 0.842 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.45
PhyloP100		0.53
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: rs4843713; hg19: chr16-87872844;