Genetic Variant NM_003486.7:c.1141-59G>A (chr16-87836706-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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.291

Publications

6 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=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A5	NM_003486.7 link	c.1141-59G>A		intron_variant	Intron 7 of 9	ENST00000261622.5	NP_003477.4	Q01650
SLC7A5-AS1	XR_007065175.1 link	n.442C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A5	ENST00000261622.5 link	c.1141-59G>A		intron_variant	Intron 7 of 9	1	NM_003486.7	ENSP00000261622.4		Q01650

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39824

AN:

152044

Hom.:

5504

Cov.:

show subpopulations

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.:

AF XY:

0.251

AC XY:

180065

AN XY:

716452

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14747

29493

44240

58986

73733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8756

17512

26268

35024

43780

<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:

0.262

AC:

39875

AN:

152162

Hom.:

5521

Cov.:

AF XY:

0.262

AC XY:

19506

AN XY:

74388

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.251

AC:

17049

AN:

67978

Other (OTH)

AF:

0.241

AC:

510

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1503

3006

4508

6011

7514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.276

Hom.:

748

Bravo

AF:

0.261

Asia WGS

AF:

0.193

AC:

673

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.19

(source)

DANN

Benign

0.60

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over