Variant 5-154793910-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_033551.3(LARP1):c.979A>T(p.Ser327Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000898 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

LARP1
NM_033551.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, LARP1

BS2

High AC in GnomAd at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LARP1	NM_033551.3 linkuse as main transcript	c.979A>T	p.Ser327Cys	missense_variant	6/19	ENST00000518297.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARP1	ENST00000518297.6 linkuse as main transcript	c.979A>T	p.Ser327Cys	missense_variant	6/19	5	NM_033551.3	P3	Q6PKG0-1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000757

AC:

AN:

250976

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135722

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:

0.000150

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000910

AC:

133

AN:

1461824

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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 submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.748A>T (p.S250C) alteration is located in exon 6 (coding exon 6) of the LARP1 gene. This alteration results from a A to T substitution at nucleotide position 748, causing the serine (S) at amino acid position 250 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

0.045

BayesDel_noAF

Uncertain

0.10

Cadd

Pathogenic

Dann

Uncertain

0.99

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.082

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.64

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.021

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.81

MVP

0.49

MPC

1.6

ClinPred

0.46

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

gMVP

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over