rs80283711

Variant names:

• chr19-32830681-G-A
• rs80283711
• NM_014270.5:c.1403C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-32830681-G-A
• chr19-32830681-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014270.5(SLC7A9):​c.1403C>T​(p.Pro468Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00104 in 1,613,602 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P468S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (14 hom.)
• Consequence: SLC7A9 NM_014270.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:3
• Conservation: PhyloP100: 7.00
• Publications: 9 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008548379).
• BP6: Variant 19-32830681-G-A is Benign according to our data. Variant chr19-32830681-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 328743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00109 (166/152292) while in subpopulation EAS AF = 0.00772 (40/5180). AF 95% confidence interval is 0.00583. There are 1 homozygotes in GnomAd4. There are 89 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR,AD,SD gene

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.1403C>T	p.Pro468Leu	missense	Exon 13 of 13	NP_055085.1	P82251
	SLC7A9	NM_001126335.2		c.1403C>T	p.Pro468Leu	missense	Exon 13 of 13	NP_001119807.1	P82251
	SLC7A9	NM_001243036.2		c.1403C>T	p.Pro468Leu	missense	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.1403C>T	p.Pro468Leu	missense	Exon 13 of 13	ENSP00000023064.3	P82251
	SLC7A9	ENST00000587772.1	TSL:1	c.1403C>T	p.Pro468Leu	missense	Exon 13 of 13	ENSP00000468439.1	P82251
	SLC7A9	ENST00000590341.5	TSL:1	c.1403C>T	p.Pro468Leu	missense	Exon 13 of 13	ENSP00000464822.1	P82251

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 164 AN: 152174 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00770

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00317 AC: 797 AN: 251482 AF XY: 0.00260

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00696

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00104 AC: 1518 AN: 1461310 Hom.: 14 Cov.: 30 AF XY: 0.00102 AC XY: 745 AN XY: 726992

African (AFR) AF: 0.0000299 AC: 1 AN: 33460

American (AMR) AF: 0.0167 AC: 746 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0130 AC: 517 AN: 39686

South Asian (SAS) AF: 0.00179 AC: 154 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1111532

Other (OTH) AF: 0.000812 AC: 49 AN: 60376

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152292 Hom.: 1 Cov.: 33 AF XY: 0.00120 AC XY: 89 AN XY: 74458

African (AFR) AF: 0.000144 AC: 6 AN: 41558

American (AMR) AF: 0.00667 AC: 102 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00772 AC: 40 AN: 5180

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000958 Hom.: 1

Bravo AF: 0.00176

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00273 AC: 332

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
1	-	1	Cystinuria (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Uncertain	0.12
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.019
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0085	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.54
Sift	Benign	0.62	T
Sift4G	Benign	0.48	T
Polyphen		0.15	B
Vest4		0.67
MVP		0.91
MPC		0.55
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.13
gMVP		0.65
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs80283711; hg19: chr19-33321587; COSMIC: COSV50084637; COSMIC: COSV50084637;