Genetic Variant SLC7A5:c.*438C>G (chr16-87832532-G-C) – 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.*438C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 153,570 control chromosomes in the GnomAD database, including 5,775 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 0.25 ( 5705 hom., cov: 31)

Exomes 𝑓: 0.26 ( 70 hom. )

Consequence

SLC7A5
NM_003486.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32

Publications

28 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=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A5	NM_003486.7 link	c.*438C>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000261622.5	NP_003477.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A5	ENST00000261622.5 link	c.*438C>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_003486.7	ENSP00000261622.4

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38492

AN:

151882

Hom.:

5703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.259

AC:

407

AN:

1570

Hom.:

Cov.:

AF XY:

0.257

AC XY:

224

AN XY:

872

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.360

AC:

AN:

228

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

AN:

East Asian (EAS)

AF:

0.615

AC:

AN:

South Asian (SAS)

AF:

0.218

AC:

AN:

110

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.237

AC:

263

AN:

1108

Other (OTH)

AF:

0.274

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.253

AC:

38501

AN:

152000

Hom.:

5705

Cov.:

AF XY:

0.257

AC XY:

19062

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.133

AC:

5524

AN:

41492

American (AMR)

AF:

0.377

AC:

5759

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

753

AN:

3472

East Asian (EAS)

AF:

0.592

AC:

3045

AN:

5146

South Asian (SAS)

AF:

0.196

AC:

946

AN:

4822

European-Finnish (FIN)

AF:

0.276

AC:

2912

AN:

10568

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18803

AN:

67898

Other (OTH)

AF:

0.250

AC:

528

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1387

2774

4161

5548

6935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.272

Hom.:

864

Bravo

AF:

0.259

Asia WGS

AF:

0.380

AC:

1320

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.41

(source)

DANN

Benign

0.51

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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