Genetic Variant SLC7A9:c.88-1209A>G (chr19-32865985-T-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_014270.5(SLC7A9):c.88-1209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 149,520 control chromosomes in the GnomAD database, including 10,687 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 0.37 ( 10687 hom., cov: 28)

Consequence

SLC7A9
NM_014270.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0440

Publications

54 publications found

Variant links:

Genes affected

SLC7A9 (HGNC:11067): (solute carrier family 7 member 9) This gene encodes a protein that belongs to a family of light subunits of amino acid transporters. This protein plays a role in the high-affinity and sodium-independent transport of cystine and neutral and dibasic amino acids, and appears to function in the reabsorption of cystine in the kidney tubule. Mutations in this gene cause non-type I cystinuria, a disease that leads to cystine stones in the urinary system due to impaired transport of cystine and dibasic amino acids. Alternate transcript variants, which encode the same protein, have been found for this gene. [provided by RefSeq, Jul 2011]

SLC7A9 Gene-Disease associations (from GenCC):

cystinuria
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
cystinuria type B
Inheritance: SD Classification: SUPPORTIVE Submitted by: Orphanet

SLC7A9 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014270.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC7A9	NM_014270.5	MANE Select	c.88-1209A>G	intron	N/A	NP_055085.1	P82251
SLC7A9	NM_001126335.2		c.88-1209A>G	intron	N/A	NP_001119807.1	P82251
SLC7A9	NM_001243036.2		c.88-1209A>G	intron	N/A	NP_001229965.1	P82251

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC7A9	ENST00000023064.9	TSL:1 MANE Select	c.88-1209A>G	intron	N/A	ENSP00000023064.3	P82251
SLC7A9	ENST00000587772.1	TSL:1	c.88-1209A>G	intron	N/A	ENSP00000468439.1	P82251
SLC7A9	ENST00000590341.5	TSL:1	c.88-1209A>G	intron	N/A	ENSP00000464822.1	P82251

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55022

AN:

149440

Hom.:

10690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.664

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.426

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

GnomAD4 genome

AF:

0.368

AC:

55026

AN:

149520

Hom.:

10687

Cov.:

AF XY:

0.368

AC XY:

26717

AN XY:

72686

show subpopulations

African (AFR)

AF:

0.278

AC:

11276

AN:

40530

American (AMR)

AF:

0.385

AC:

5766

AN:

14982

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

1839

AN:

3458

East Asian (EAS)

AF:

0.664

AC:

3348

AN:

5042

South Asian (SAS)

AF:

0.435

AC:

2069

AN:

4754

European-Finnish (FIN)

AF:

0.303

AC:

2951

AN:

9754

Middle Eastern (MID)

AF:

0.500

AC:

145

AN:

290

European-Non Finnish (NFE)

AF:

0.389

AC:

26311

AN:

67716

Other (OTH)

AF:

0.422

AC:

879

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1606

3213

4819

6426

8032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.392

Hom.:

42870

Bravo

AF:

0.375

Asia WGS

AF:

0.482

AC:

1678

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.7

(source)

DANN

Benign

0.55

PhyloP100

-0.044

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over