2-44312754-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_000341.4(SLC3A1):​c.1500+1G>C variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.000000686 in 1,456,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC3A1
NM_000341.4 splice_donor, intron

Scores

1
6
1
Splicing: ADA: 1.000
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.33
Variant links:
Genes affected
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.08163265 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC3A1NM_000341.4 linkc.1500+1G>C splice_donor_variant, intron_variant Intron 8 of 9 ENST00000260649.11 NP_000332.2 Q07837-1A0A0S2Z4E1
SLC3A1XM_011533047.4 linkc.1500+1G>C splice_donor_variant, intron_variant Intron 8 of 9 XP_011531349.1 B8ZZK1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC3A1ENST00000260649.11 linkc.1500+1G>C splice_donor_variant, intron_variant Intron 8 of 9 1 NM_000341.4 ENSP00000260649.6 Q07837-1
ENSG00000285542ENST00000649044.1 linkn.*1511+1G>C splice_donor_variant, intron_variant Intron 13 of 14 ENSP00000497083.1 A0A3B3IS24

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1456836
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
724978
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.64
D
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
34
DANN
Uncertain
0.99
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Uncertain
0.15
D
ClinPred
0.89
D
GERP RS
5.8

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.94
SpliceAI score (max)
1.0
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.76
Position offset: 44
DS_DL_spliceai
1.0
Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-44539893; API