Genetic Variant SLC7A5:c.*1282G>A (chr16-87831688-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003486.7(SLC7A5):c.*1282G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,138 control chromosomes in the GnomAD database, including 8,061 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 0.32 ( 8056 hom., cov: 33)

Exomes 𝑓: 0.47 ( 5 hom. )

Consequence

SLC7A5
NM_003486.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

15 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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SLC7A5 links:

ENSG00000260466 (HGNC:58301):

ENSG00000260466 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A5	NM_003486.7 link	c.*1282G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000261622.5	NP_003477.4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLC7A5	ENST00000261622.5 link	c.*1282G>A	3_prime_UTR_variant	Exon 10 of 10	1	NM_003486.7	ENSP00000261622.4
SLC7A5	ENST00000565644.6 link	c.*1282G>A	3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000454323.1
SLC7A5	ENST00000850914.1 link	c.*1282G>A	3_prime_UTR_variant	Exon 10 of 10			ENSP00000520997.1
ENSG00000260466	ENST00000825115.1 link	n.248-5725C>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48140

AN:

151982

Hom.:

8046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.296

GnomAD4 exome

AF:

0.474

AC:

AN:

Hom.:

Cov.:

AF XY:

0.409

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.409

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.317

AC:

48177

AN:

152100

Hom.:

8056

Cov.:

AF XY:

0.320

AC XY:

23757

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.348

AC:

14463

AN:

41508

American (AMR)

AF:

0.404

AC:

6170

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

728

AN:

3470

East Asian (EAS)

AF:

0.590

AC:

3040

AN:

5150

South Asian (SAS)

AF:

0.215

AC:

1034

AN:

4820

European-Finnish (FIN)

AF:

0.284

AC:

3008

AN:

10588

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18877

AN:

67970

Other (OTH)

AF:

0.295

AC:

621

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1655

3311

4966

6622

8277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.303

Hom.:

1097

Bravo

AF:

0.330

Asia WGS

AF:

0.406

AC:

1411

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.6

(source)

DANN

Benign

0.88

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over