16-87834422-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003486.7(SLC7A5):c.1460A>G(p.Gln487Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,554,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SLC7A5
NM_003486.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

Publications

0 publications found

Variant links:

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 links:

SLC7A5-AS1 (HGNC:58301):

SLC7A5-AS1 links:

MIR6775 (HGNC:50100): (microRNA 6775) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6775 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10969758).

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.1460A>G	p.Gln487Arg	missense	Exon 9 of 10	NP_003477.4
	MIR6775	NR_106833.1		n.*170A>G		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC7A5	ENST00000261622.5	TSL:1 MANE Select	c.1460A>G	p.Gln487Arg	missense	Exon 9 of 10	ENSP00000261622.4	Q01650
SLC7A5	ENST00000565644.6	TSL:1	c.662A>G	p.Gln221Arg	missense	Exon 9 of 10	ENSP00000454323.1	A0A0C4DGL4
SLC7A5	ENST00000850914.1		c.1514A>G	p.Gln505Arg	missense	Exon 9 of 10	ENSP00000520997.1	A0ABJ7H8K0

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000624

AC:

AN:

160286

AF XY:

0.0000710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000401

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000114

AC:

AN:

1401832

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

691646

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31900

American (AMR)

AF:

0.000390

AC:

AN:

35866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25190

East Asian (EAS)

AF:

0.00

AC:

AN:

36190

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1080400

Other (OTH)

AF:

0.00

AC:

AN:

58156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41434

American (AMR)

AF:

0.000196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0018

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.32

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.64

M_CAP

Benign

0.032

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.79

PhyloP100

3.0

PrimateAI

Benign

0.33

PROVEAN

Benign

0.24

REVEL

Benign

0.24

Sift

Benign

1.0

Sift4G

Benign

0.68

Polyphen

0.064

Vest4

0.29

MutPred

0.47

Gain of MoRF binding (P = 0.0134)

MVP

0.74

MPC

0.78

ClinPred

0.042

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.056

gMVP

0.65

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over