2-44318877-C-T

Variant names:

• chr2-44318877-C-T
• rs8410
• NM_001171613.2:c.*2479G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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, Labcorp Genetics (formerly Invitae), ClinGen
• cystinuria type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285542 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PREPL	NM_001171613.2	c.*2479G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000409411.6	NP_001165084.1
SLC3A1	NM_000341.4	c.1618-1322C>T		intron_variant	Intron 9 of 9	ENST00000260649.11	NP_000332.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREPL	ENST00000409411.6	c.*2479G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_001171613.2	ENSP00000387095.2
SLC3A1	ENST00000260649.11	c.1618-1322C>T		intron_variant	Intron 9 of 9	1	NM_000341.4	ENSP00000260649.6
ENSG00000285542	ENST00000649044.1	n.*1629-1322C>T		intron_variant	Intron 14 of 14			ENSP00000497083.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.837 AC: 34741 AN: 41520

American (AMR) AF: 0.686 AC: 10467 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2711 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1581 AN: 5170

South Asian (SAS) AF: 0.653 AC: 3149 AN: 4820

European-Finnish (FIN) AF: 0.688 AC: 7273 AN: 10568

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53766 AN: 67986

Other (OTH) AF: 0.753 AC: 1591 AN: 2112

Alfa AF: 0.760 Hom.: 24913

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
PhyloP100		-0.42
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: rs8410; hg19: chr2-44546016;