5-154793985-C-T

Variant names:

• chr5-154793985-C-T
• rs780627190
• NM_033551.3:c.1054C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_033551.3(LARP1):​c.1054C>T​(p.Arg352Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 1.82
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP1	NM_033551.3	MANE Select	c.1054C>T	p.Arg352Trp	missense	Exon 6 of 19	NP_291029.2
	LARP1	NM_015315.6		c.823C>T	p.Arg275Trp	missense	Exon 6 of 19	NP_056130.2
	LARP1	NM_001367713.1		c.439C>T	p.Arg147Trp	missense	Exon 6 of 19	NP_001354642.1	A0A8I5KWU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP1	ENST00000518297.6	TSL:5 MANE Select	c.1054C>T	p.Arg352Trp	missense	Exon 6 of 19	ENSP00000428589.2	Q6PKG0-1
	LARP1	ENST00000336314.9	TSL:1	c.823C>T	p.Arg275Trp	missense	Exon 6 of 19	ENSP00000336721.4	Q6PKG0-3
	LARP1	ENST00000913421.1		c.1054C>T	p.Arg352Trp	missense	Exon 6 of 19	ENSP00000583480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000808 AC: 2 AN: 247450 AF XY: 0.00000747

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458076 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724716

African (AFR) AF: 0.00 AC: 0 AN: 33356

American (AMR) AF: 0.0000225 AC: 1 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 86018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109480

Other (OTH) AF: 0.00 AC: 0 AN: 60208

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.81	T
PhyloP100		1.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.38		Loss of solvent accessibility (P = 0.0023)
MVP		0.45
MPC		1.7
ClinPred		0.97	D
GERP RS		5.8
PromoterAI		0.0070	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.8
gMVP		0.57
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs780627190; hg19: chr5-154173545; COSMIC: COSV60431803; COSMIC: COSV60431803;