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GeneBe

5-154802245-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_033551.3(LARP1):c.1955A>G(p.Tyr652Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LARP1
NM_033551.3 missense

Scores

2
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97
Variant links:
Genes affected
LARP1 (HGNC:29531): (La ribonucleoprotein 1, translational regulator) Enables eukaryotic initiation factor 4E binding activity; nucleic acid binding activity; and ribosomal small subunit binding activity. Involved in several processes, including TORC1 signaling; cellular response to rapamycin; and posttranscriptional regulation of gene expression. Located in cytoplasmic stress granule. Colocalizes with TORC1 complex and polysomal ribosome. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, LARP1
BP4
Computational evidence support a benign effect (MetaRNN=0.39770028).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LARP1NM_033551.3 linkuse as main transcriptc.1955A>G p.Tyr652Cys missense_variant 11/19 ENST00000518297.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LARP1ENST00000518297.6 linkuse as main transcriptc.1955A>G p.Tyr652Cys missense_variant 11/195 NM_033551.3 P3Q6PKG0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 29, 2023The c.1724A>G (p.Y575C) alteration is located in exon 11 (coding exon 11) of the LARP1 gene. This alteration results from a A to G substitution at nucleotide position 1724, causing the tyrosine (Y) at amino acid position 575 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.098
D
BayesDel_noAF
Benign
-0.10
Cadd
Pathogenic
26
Dann
Uncertain
0.99
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-2.5
D;D;D
REVEL
Benign
0.17
Sift
Benign
0.11
T;T;T
Sift4G
Benign
0.12
T;T;T
Polyphen
0.52
P;.;.
Vest4
0.76
MutPred
0.36
.;Loss of phosphorylation at Y652 (P = 0.0521);.;
MVP
0.22
MPC
1.8
ClinPred
0.94
D
GERP RS
6.2
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.8
gMVP
0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-154181805; API