chr19-32830538-G-A

Variant names:

• chr19-32830538-G-A
• rs537630298
• NM_014270.5:c.*82C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_014270.5(SLC7A9):​c.*82C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0006 in 1,052,376 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00051 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00062 (1 hom.)
• Consequence: SLC7A9 NM_014270.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.491
• Publications: 1 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
• cystinuria type B

  Inheritance: SD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.000615 (554/900232) while in subpopulation SAS AF = 0.00205 (153/74638). AF 95% confidence interval is 0.00178. There are 1 homozygotes in GnomAdExome4. There are 313 alleles in the male GnomAdExome4 subpopulation. Median coverage is 12. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A9	NM_014270.5	MANE Select	c.*82C>T		3_prime_UTR	Exon 13 of 13	NP_055085.1	P82251
	SLC7A9	NM_001126335.2		c.*82C>T		3_prime_UTR	Exon 13 of 13	NP_001119807.1	P82251
	SLC7A9	NM_001243036.2		c.*82C>T		3_prime_UTR	Exon 13 of 13	NP_001229965.1	P82251

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A9	ENST00000023064.9	TSL:1 MANE Select	c.*82C>T		3_prime_UTR	Exon 13 of 13	ENSP00000023064.3	P82251
	SLC7A9	ENST00000590341.5	TSL:1	c.*82C>T		3_prime_UTR	Exon 13 of 13	ENSP00000464822.1	P82251
	SLC7A9	ENST00000879205.1		c.*82C>T		3_prime_UTR	Exon 13 of 13	ENSP00000549264.1

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152026 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000615 AC: 554 AN: 900232 Hom.: 1 Cov.: 12 AF XY: 0.000663 AC XY: 313 AN XY: 471836

African (AFR) AF: 0.000222 AC: 5 AN: 22494

American (AMR) AF: 0.000367 AC: 16 AN: 43600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22540

East Asian (EAS) AF: 0.00 AC: 0 AN: 36958

South Asian (SAS) AF: 0.00205 AC: 153 AN: 74638

European-Finnish (FIN) AF: 0.000208 AC: 11 AN: 52768

Middle Eastern (MID) AF: 0.000878 AC: 3 AN: 3418

European-Non Finnish (NFE) AF: 0.000571 AC: 344 AN: 602128

Other (OTH) AF: 0.000528 AC: 22 AN: 41688

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152144 Hom.: 1 Cov.: 33 AF XY: 0.000592 AC XY: 44 AN XY: 74374

African (AFR) AF: 0.000289 AC: 12 AN: 41514

American (AMR) AF: 0.00111 AC: 17 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000529 Hom.: 0

Bravo AF: 0.000408

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Cystinuria (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.80
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism

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: rs537630298; hg19: chr19-33321444; COSMIC: COSV50092178; COSMIC: COSV50092178;