Genetic Variant LARP4B:p.Pro734Arg (chr10-812942-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015155.3(LARP4B):c.2201C>G(p.Pro734Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000187 in 1,547,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

LARP4B
NM_015155.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34

Publications

2 publications found

Variant links:

Genes affected

LARP4B (HGNC:28987): (La ribonucleoprotein 4B) This gene encodes a member of an evolutionarily conserved protein family implicated in RNA metabolism and translation. Members of this family are characterized by the presence of an La motif, which is often located adjacent to one or more RNA recognition motifs (RRM). Together, the two motifs constitute the functional region of the protein and enable its interaction with the RNA substrate. This protein family is divided into five sub-families: the genuine La proteins and four La-related protein (LARP) sub-families. The protein encoded by this gene belongs to LARP sub-family 4. It is a cytoplasmic protein that may play a stimulatory role in translation. [provided by RefSeq, Oct 2012]

LARP4B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARP4B	NM_015155.3 link	c.2201C>G	p.Pro734Arg	missense_variant	Exon 18 of 18	ENST00000316157.8	NP_055970.1	Q92615

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARP4B	ENST00000316157.8 link	c.2201C>G	p.Pro734Arg	missense_variant	Exon 18 of 18	1	NM_015155.3	ENSP00000326128.3		Q92615

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000208

AC:

AN:

192128

AF XY:

0.0000290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000470

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1395746

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

690720

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30458

American (AMR)

AF:

0.0000337

AC:

AN:

29716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21520

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39314

South Asian (SAS)

AF:

0.0000133

AC:

AN:

75004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4014

European-Non Finnish (NFE)

AF:

0.0000193

AC:

AN:

1088064

Other (OTH)

AF:

0.0000174

AC:

AN:

57358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000264

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2201C>G (p.P734R) alteration is located in exon 17 (coding exon 17) of the LARP4B gene. This alteration results from a C to G substitution at nucleotide position 2201, causing the proline (P) at amino acid position 734 to be replaced by an arginine (R). 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

Benign

0.12

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;.

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.42

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Pathogenic

3.1

.;M;M

PhyloP100

6.3

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.7

.;.;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0020

.;.;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.99

.;D;D

Vest4

0.78, 0.80

MutPred

0.37

.;Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);

MVP

0.35

MPC

1.0

ClinPred

0.84

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.56

gMVP

0.41

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-812942-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over