Genetic Variant LARP1:p.Pro301Ala (chr5-154793832-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033551.3(LARP1):c.901C>G(p.Pro301Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P301T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LARP1
NM_033551.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.115

Publications

0 publications found

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]

LARP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.099184036).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033551.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LARP1	NM_033551.3	MANE Select	c.901C>G	p.Pro301Ala	missense	Exon 6 of 19	NP_291029.2
LARP1	NM_001367718.1		c.901C>G	p.Pro301Ala	missense	Exon 6 of 19	NP_001354647.1
LARP1	NM_015315.6		c.670C>G	p.Pro224Ala	missense	Exon 6 of 19	NP_056130.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LARP1	ENST00000518297.6	TSL:5 MANE Select	c.901C>G	p.Pro301Ala	missense	Exon 6 of 19	ENSP00000428589.2	Q6PKG0-1
LARP1	ENST00000336314.9	TSL:1	c.670C>G	p.Pro224Ala	missense	Exon 6 of 19	ENSP00000336721.4	Q6PKG0-3
LARP1	ENST00000913421.1		c.901C>G	p.Pro301Ala	missense	Exon 6 of 19	ENSP00000583480.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.65

M_CAP

Benign

0.0042

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.0

PhyloP100

-0.12

PrimateAI

Benign

0.44

PROVEAN

Benign

0.050

REVEL

Benign

0.036

Sift

Benign

0.81

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.25

MutPred

0.25

Loss of catalytic residue at P301 (P = 0.0151)

MVP

0.28

MPC

0.60

ClinPred

0.026

GERP RS

2.2

PromoterAI

0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.1

gMVP

0.16

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over