chr19-32865985-T-C

Variant names:

• chr19-32865985-T-C
• rs12460876
• NM_014270.5:c.88-1209A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 54 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
• cystinuria type B

  Inheritance: SD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A9	NM_014270.5	c.88-1209A>G		intron_variant	Intron 2 of 12	ENST00000023064.9	NP_055085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A9	ENST00000023064.9	c.88-1209A>G		intron_variant	Intron 2 of 12	1	NM_014270.5	ENSP00000023064.3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55022 AN: 149440 Hom.: 10690 Cov.: 28

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.: 28 AF XY: 0.368 AC XY: 26717 AN XY: 72686

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.55
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12460876; hg19: chr19-33356891;