2-44318877-C-T

Position:

• chr2-44318877-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171613.2(PREPL):​c.*2479G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,116 control chromosomes in the GnomAD database, including 45,350 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (45350 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PREPL NM_001171613.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREPL	NM_001171613.2	c.*2479G>A		3_prime_UTR_variant	14/14	ENST00000409411.6	NP_001165084.1
SLC3A1	NM_000341.4	c.1618-1322C>T		intron_variant		ENST00000260649.11	NP_000332.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREPL	ENST00000409411.6	c.*2479G>A		3_prime_UTR_variant	14/14	1	NM_001171613.2	ENSP00000387095	P4
SLC3A1	ENST00000260649.11	c.1618-1322C>T		intron_variant		1	NM_000341.4	ENSP00000260649	P1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116235 AN: 151998 Hom.: 45326 Cov.: 32

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.760

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.765 AC: 116302 AN: 152116 Hom.: 45350 Cov.: 32 AF XY: 0.753 AC XY: 56026 AN XY: 74358

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.753

Alfa AF: 0.769 Hom.: 14397

Bravo AF: 0.765

Asia WGS AF: 0.516 AC: 1797 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.41
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: rs8410; hg19: chr2-44546016;