5-154793985-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2

The NM_033551.3(LARP1):​c.1054C>T​(p.Arg352Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

LARP1
NM_033551.3 missense

Scores

4
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LARP1NM_033551.3 linkuse as main transcriptc.1054C>T p.Arg352Trp missense_variant 6/19 ENST00000518297.6 NP_291029.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LARP1ENST00000518297.6 linkuse as main transcriptc.1054C>T p.Arg352Trp missense_variant 6/195 NM_033551.3 ENSP00000428589 P3Q6PKG0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000808
AC:
2
AN:
247450
Hom.:
0
AF XY:
0.00000747
AC XY:
1
AN XY:
133800
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000548
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000343
AC:
5
AN:
1458076
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
724716
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000247
AC:
3

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 GeneticsApr 22, 2024The c.823C>T (p.R275W) alteration is located in exon 6 (coding exon 6) of the LARP1 gene. This alteration results from a C to T substitution at nucleotide position 823, causing the arginine (R) at amino acid position 275 to be replaced by a tryptophan (W). 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
0.035
T
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
.;.;T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.47
T;T;T
MetaSVM
Benign
-0.81
T
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-4.4
D;D;D
REVEL
Benign
0.19
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.74
MutPred
0.38
.;Loss of solvent accessibility (P = 0.0023);.;
MVP
0.45
MPC
1.7
ClinPred
0.97
D
GERP RS
5.8
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.8
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780627190; hg19: chr5-154173545; COSMIC: COSV60431803; COSMIC: COSV60431803; API