chr19-32830811-A-AGG

Variant names:

• chr19-32830811-A-AGG
• rs10645053
• NM_014270.5:c.1400-129_1400-128dupCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014270.5(SLC7A9):​c.1400-129_1400-128dupCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 751,580 control chromosomes in the GnomAD database, including 119,485 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (27596 hom., cov: 0)
  • Exomes 𝑓: 0.54 (91889 hom.)
• Consequence: SLC7A9 NM_014270.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.675
• 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: AD, AR 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 -10 ACMG points.

• BP6: Variant 19-32830811-A-AGG is Benign according to our data. Variant chr19-32830811-A-AGG is described in ClinVar as Benign. ClinVar VariationId is 1295545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A9	NM_014270.5	MANE Select	c.1400-129_1400-128dupCC		intron	N/A	NP_055085.1	P82251
	SLC7A9	NM_001126335.2		c.1400-129_1400-128dupCC		intron	N/A	NP_001119807.1	P82251
	SLC7A9	NM_001243036.2		c.1400-129_1400-128dupCC		intron	N/A	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.1400-128_1400-127insCC		intron	N/A	ENSP00000023064.3	P82251
	SLC7A9	ENST00000587772.1	TSL:1	c.1400-128_1400-127insCC		intron	N/A	ENSP00000468439.1	P82251
	SLC7A9	ENST00000590341.5	TSL:1	c.1400-128_1400-127insCC		intron	N/A	ENSP00000464822.1	P82251

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89980 AN: 151924 Hom.: 27553 Cov.: 0

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.545 AC: 326507 AN: 599538 Hom.: 91889 AF XY: 0.543 AC XY: 175029 AN XY: 322230

African (AFR) AF: 0.734 AC: 12450 AN: 16970

American (AMR) AF: 0.460 AC: 15993 AN: 34802

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 11880 AN: 19642

East Asian (EAS) AF: 0.857 AC: 28048 AN: 32710

South Asian (SAS) AF: 0.531 AC: 34222 AN: 64490

European-Finnish (FIN) AF: 0.528 AC: 23140 AN: 43852

Middle Eastern (MID) AF: 0.609 AC: 2472 AN: 4060

European-Non Finnish (NFE) AF: 0.513 AC: 180352 AN: 351470

Other (OTH) AF: 0.569 AC: 17950 AN: 31542

GnomAD4 genome AF: 0.592 AC: 90073 AN: 152042 Hom.: 27596 Cov.: 0 AF XY: 0.592 AC XY: 43972 AN XY: 74304

African (AFR) AF: 0.734 AC: 30461 AN: 41504

American (AMR) AF: 0.509 AC: 7765 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2091 AN: 3468

East Asian (EAS) AF: 0.822 AC: 4249 AN: 5168

South Asian (SAS) AF: 0.537 AC: 2581 AN: 4804

European-Finnish (FIN) AF: 0.536 AC: 5669 AN: 10576

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.519 AC: 35240 AN: 67958

Other (OTH) AF: 0.605 AC: 1275 AN: 2106

Alfa AF: 0.627 Hom.: 2825

Bravo AF: 0.600

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10645053; hg19: chr19-33321717;