5-154793941-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_033551.3(LARP1):ā€‹c.1010T>Cā€‹(p.Phe337Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000353 in 1,613,604 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.000033 ( 0 hom. )

Consequence

LARP1
NM_033551.3 missense

Scores

2
1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77
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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.19314486).
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LARP1NM_033551.3 linkuse as main transcriptc.1010T>C p.Phe337Ser 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.1010T>C p.Phe337Ser missense_variant 6/195 NM_033551.3 ENSP00000428589.2 Q6PKG0-1A0A0B4J210

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
249868
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135236
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000444
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000328
AC:
48
AN:
1461452
Hom.:
0
Cov.:
32
AF XY:
0.0000275
AC XY:
20
AN XY:
726986
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000405
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000774
Hom.:
0
Bravo
AF:
0.0000416
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 GeneticsJul 12, 2023The c.779T>C (p.F260S) alteration is located in exon 6 (coding exon 6) of the LARP1 gene. This alteration results from a T to C substitution at nucleotide position 779, causing the phenylalanine (F) at amino acid position 260 to be replaced by a serine (S). 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
Benign
-0.064
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.028
.;.;T
Eigen
Benign
0.0045
Eigen_PC
Benign
0.21
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.81
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.088
Sift
Benign
0.14
T;T;T
Sift4G
Benign
0.26
T;T;T
Polyphen
0.035
B;.;.
Vest4
0.66
MVP
0.17
MPC
1.4
ClinPred
0.17
T
GERP RS
5.8
gMVP
0.41

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

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

Other links and lift over

dbSNP: rs776372021; hg19: chr5-154173501; API