2-44320003-A-G

Position:

• chr2-44320003-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001171613.2(PREPL):​c.*1353T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 584,174 control chromosomes in the GnomAD database, including 2,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.083 (603 hom., cov: 33)
  • Exomes 𝑓: 0.083 (1797 hom.)
• Consequence: PREPL NM_001171613.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.79

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-44320003-A-G is Benign according to our data. Variant chr2-44320003-A-G is described in ClinVar as [Benign]. Clinvar id is 1228567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PREPL	NM_001171613.2	c.*1353T>C		3_prime_UTR_variant	14/14	ENST00000409411.6
SLC3A1	NM_000341.4	c.1618-196A>G		intron_variant		ENST00000260649.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PREPL	ENST00000409411.6	c.*1353T>C		3_prime_UTR_variant	14/14	1	NM_001171613.2	P4
SLC3A1	ENST00000260649.11	c.1618-196A>G		intron_variant		1	NM_000341.4	P1

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12675 AN: 152164 Hom.: 604 Cov.: 33

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0851

GnomAD4 exome AF: 0.0830 AC: 35846 AN: 431892 Hom.: 1797 Cov.: 4 AF XY: 0.0790 AC XY: 18196 AN XY: 230252

Gnomad4 AFR exome AF: 0.0597

Gnomad4 AMR exome AF: 0.0627

Gnomad4 ASJ exome AF: 0.0802

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0187

Gnomad4 FIN exome AF: 0.0954

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0859

GnomAD4 genome AF: 0.0832 AC: 12677 AN: 152282 Hom.: 603 Cov.: 33 AF XY: 0.0827 AC XY: 6162 AN XY: 74468

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.0703

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0842

Alfa AF: 0.0936 Hom.: 710

Bravo AF: 0.0818

Asia WGS AF: 0.0180 AC: 64 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3197473; hg19: chr2-44547142;