19-32833074-G-T

Position:

• chr19-32833074-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014270.5(SLC7A9):​c.1399+75C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,385,168 control chromosomes in the GnomAD database, including 902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (80 hom., cov: 32)
  • Exomes 𝑓: 0.032 (822 hom.)
• Consequence: SLC7A9 NM_014270.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0960

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-32833074-G-T is Benign according to our data. Variant chr19-32833074-G-T is described in ClinVar as [Benign]. Clinvar id is 1297408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0222 (3382/152364) while in subpopulation NFE AF= 0.0327 (2225/68034). AF 95% confidence interval is 0.0316. There are 80 homozygotes in gnomad4. There are 1611 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 80 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A9	NM_014270.5	c.1399+75C>A		intron_variant		ENST00000023064.9	NP_055085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A9	ENST00000023064.9	c.1399+75C>A		intron_variant		1	NM_014270.5	ENSP00000023064	P1
	ENST00000590069.1	n.341G>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3384 AN: 152246 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.00564

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0206

GnomAD4 exome AF: 0.0319 AC: 39271 AN: 1232804 Hom.: 822 Cov.: 18 AF XY: 0.0311 AC XY: 19408 AN XY: 624794

Gnomad4 AFR exome AF: 0.00467

Gnomad4 AMR exome AF: 0.00933

Gnomad4 ASJ exome AF: 0.00408

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00828

Gnomad4 FIN exome AF: 0.0545

Gnomad4 NFE exome AF: 0.0373

Gnomad4 OTH exome AF: 0.0239

GnomAD4 genome AF: 0.0222 AC: 3382 AN: 152364 Hom.: 80 Cov.: 32 AF XY: 0.0216 AC XY: 1611 AN XY: 74512

Gnomad4 AFR AF: 0.00563

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00600

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0327

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0258 Hom.: 11

Bravo AF: 0.0195

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs150281357; hg19: chr19-33323980;