5-154799897-C-T

Position:

• chr5-154799897-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_033551.3(LARP1):​c.1571C>T​(p.Ala524Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,726 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• 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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06750238).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP1	NM_033551.3	c.1571C>T	p.Ala524Val	missense_variant	10/19	ENST00000518297.6	NP_291029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP1	ENST00000518297.6	c.1571C>T	p.Ala524Val	missense_variant	10/19	5	NM_033551.3	ENSP00000428589	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461726 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

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

Dec 18, 2023

The c.1340C>T (p.A447V) alteration is located in exon 10 (coding exon 10) of the LARP1 gene. This alteration results from a C to T substitution at nucleotide position 1340, causing the alanine (A) at amino acid position 447 to be replaced by a valine (V). 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	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0045	.;.;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.013
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.068	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.98	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.090	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.53	T;T;T;T
Sift4G	Benign	0.32	T;T;T;T
Polyphen		0.0010	B;.;.;.
Vest4		0.25
MutPred		0.14		.;Loss of glycosylation at P522 (P = 0.1857);.;.;
MVP		0.17
MPC		0.67
ClinPred		0.34	T
GERP RS		6.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
gMVP		0.49

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

Other links and lift over

dbSNP: rs1330941178; hg19: chr5-154179457;