5-154799897-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_033551.3(LARP1):c.1571C>A(p.Ala524Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A524S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LARP1 NM_033551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 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=0.07631305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LARP1	NM_033551.3	c.1571C>A	p.Ala524Glu	missense_variant	10/19	ENST00000518297.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARP1	ENST00000518297.6	c.1571C>A	p.Ala524Glu	missense_variant	10/19	5	NM_033551.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2023

The c.1340C>A (p.A447E) alteration is located in exon 10 (coding exon 10) of the LARP1 gene. This alteration results from a C to A substitution at nucleotide position 1340, causing the alanine (A) at amino acid position 447 to be replaced by a glutamic acid (E). 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	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Uncertain	25
Dann	Benign	0.66
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.076	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.96	N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.19	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.67	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0030	B;.;.;.
Vest4		0.28
MutPred		0.18		.;Gain of solvent accessibility (P = 0.0674);.;.;
MVP		0.19
MPC		0.87
ClinPred		0.21	T
GERP RS		6.0
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr5-154179457;