rs17032122

Variant names:

• chr2-44320097-G-C
• rs17032122
• NM_001171613.2:c.*1259C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001171613.2(PREPL):​c.*1259C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,025,554 control chromosomes in the GnomAD database, including 826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (499 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (327 hom.)
• Consequence: PREPL NM_001171613.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.319
• Publications: 1 publications found

Genes affected

PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]

SLC3A1 (HGNC:11025): (solute carrier family 3 member 1) This gene encodes a type II membrane glycoprotein which is one of the components of the renal amino acid transporter which transports neutral and basic amino acids in the renal tubule and intestinal tract. Mutations and deletions in this gene are associated with cystinuria. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

SLC3A1 Gene-Disease associations (from GenCC):

• cystinuria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• cystinuria type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285542 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-44320097-G-C is Benign according to our data. Variant chr2-44320097-G-C is described in ClinVar as Benign. ClinVar VariationId is 1242368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171613.2. 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
	PREPL	NM_001171613.2	MANE Select	c.*1259C>G		3_prime_UTR	Exon 14 of 14	NP_001165084.1	Q4J6C6-4
	SLC3A1	NM_000341.4	MANE Select	c.1618-102G>C		intron	N/A	NP_000332.2	Q07837-1
	PREPL	NM_001171603.1		c.*1259C>G		3_prime_UTR	Exon 15 of 15	NP_001165074.1	Q4J6C6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PREPL	ENST00000409411.6	TSL:1 MANE Select	c.*1259C>G		3_prime_UTR	Exon 14 of 14	ENSP00000387095.2	Q4J6C6-4
	PREPL	ENST00000409936.5	TSL:1	c.*1259C>G		3_prime_UTR	Exon 15 of 15	ENSP00000386543.1	Q4J6C6-1
	SLC3A1	ENST00000260649.11	TSL:1 MANE Select	c.1618-102G>C		intron	N/A	ENSP00000260649.6	Q07837-1

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6886 AN: 152072 Hom.: 491 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.00485 AC: 4238 AN: 873364 Hom.: 327 Cov.: 12 AF XY: 0.00421 AC XY: 1876 AN XY: 446128

African (AFR) AF: 0.162 AC: 3322 AN: 20566

American (AMR) AF: 0.00931 AC: 238 AN: 25576

Ashkenazi Jewish (ASJ) AF: 0.00118 AC: 23 AN: 19482

East Asian (EAS) AF: 0.0000300 AC: 1 AN: 33298

South Asian (SAS) AF: 0.000265 AC: 16 AN: 60444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36738

Middle Eastern (MID) AF: 0.00765 AC: 22 AN: 2874

European-Non Finnish (NFE) AF: 0.000262 AC: 166 AN: 633980

Other (OTH) AF: 0.0111 AC: 450 AN: 40406

GnomAD4 genome AF: 0.0455 AC: 6918 AN: 152190 Hom.: 499 Cov.: 33 AF XY: 0.0441 AC XY: 3280 AN XY: 74402

African (AFR) AF: 0.158 AC: 6553 AN: 41504

American (AMR) AF: 0.0160 AC: 245 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000662 AC: 45 AN: 68026

Other (OTH) AF: 0.0308 AC: 65 AN: 2110

Alfa AF: 0.0365 Hom.: 45

Bravo AF: 0.0515

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs17032122; hg19: chr2-44547236;