5-154793949-C-G

Variant names:

• chr5-154793949-C-G
• rs770414206
• NM_033551.3:c.1018C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033551.3(LARP1):​c.1018C>G​(p.Arg340Gly) 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 1,461,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R340C) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3155856).

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.1018C>G	p.Arg340Gly	missense	Exon 6 of 19	NP_291029.2
	LARP1	NM_015315.6		c.787C>G	p.Arg263Gly	missense	Exon 6 of 19	NP_056130.2
	LARP1	NM_001367713.1		c.403C>G	p.Arg135Gly	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.1018C>G	p.Arg340Gly	missense	Exon 6 of 19	ENSP00000428589.2	Q6PKG0-1
	LARP1	ENST00000336314.9	TSL:1	c.787C>G	p.Arg263Gly	missense	Exon 6 of 19	ENSP00000336721.4	Q6PKG0-3
	LARP1	ENST00000913421.1		c.1018C>G	p.Arg340Gly	missense	Exon 6 of 19	ENSP00000583480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461032 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726720

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111458

Other (OTH) AF: 0.0000166 AC: 1 AN: 60348

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	0.0081	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.98	T
PhyloP100		2.1
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.25
Sift	Benign	0.086	T
Sift4G	Benign	0.069	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.40		Loss of methylation at R340 (P = 2e-04)
MVP		0.34
MPC		1.8
ClinPred		0.95	D
GERP RS		4.9
PromoterAI		0.016	Neutral
gMVP		0.61
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs770414206; hg19: chr5-154173509;