Variant 12-50430516-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052879.5(LARP4):c.344C>T(p.Ser115Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,336 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

LARP4
NM_052879.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.21

Variant links:

Genes affected

LARP4 (HGNC:24320): (La ribonucleoprotein 4) Enables mRNA 3'-UTR binding activity and poly(A) binding activity. Involved in cytoskeleton organization; positive regulation of translation; and regulation of cell morphogenesis. Located in cytosol. Colocalizes with cytoplasmic stress granule; cytosolic small ribosomal subunit; and polysome. [provided by Alliance of Genome Resources, Apr 2022]

LARP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP4	NM_052879.5 linkuse as main transcript	c.344C>T	p.Ser115Phe	missense_variant	4/16	ENST00000398473.7	NP_443111.4	Q71RC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP4	ENST00000398473.7 linkuse as main transcript	c.344C>T	p.Ser115Phe	missense_variant	4/16	1	NM_052879.5	ENSP00000381490.2		Q71RC2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247544

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454336

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723616

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000678

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000189

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

May 13, 2024

The c.344C>T (p.S115F) alteration is located in exon 4 (coding exon 4) of the LARP4 gene. This alteration results from a C to T substitution at nucleotide position 344, causing the serine (S) at amino acid position 115 to be replaced by a phenylalanine (F). 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

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

.;.;.;T;T;.;.;.;.;T;.;.;T;.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.50

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.7

.;M;.;.;M;.;M;.;.;.;.;M;.;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.9

D;D;D;D;D;.;D;.;D;D;D;D;D;D;D

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;D;D;D;D;.;D;.;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.95, 0.92, 0.90

.;.;P;.;P;.;.;.;P;.;.;.;.;.;.

Vest4

0.64, 0.65, 0.65, 0.64, 0.65, 0.66, 0.65, 0.62

MutPred

0.38

.;Gain of catalytic residue at S115 (P = 0);.;.;Gain of catalytic residue at S115 (P = 0);.;Gain of catalytic residue at S115 (P = 0);.;.;.;.;Gain of catalytic residue at S115 (P = 0);.;.;.;

MVP

0.53

MPC

0.75

ClinPred

0.99

GERP RS

4.8

Varity_R

0.53

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

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