Variant 4-128098189-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018078.4(LARP1B):c.672A>C(p.Glu224Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,453,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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

LARP1B
NM_018078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.821

Variant links:

Genes affected

LARP1B (HGNC:24704): (La ribonucleoprotein 1B) This gene encodes a protein containing domains found in the La related protein of Drosophila melanogaster. La motif-containing proteins are thought to be RNA-binding proteins, where the La motif and adjacent amino acids fold into an RNA recognition motif. The La motif is also found in proteins unrelated to the La protein. Alternative splicing has been observed at this locus and multiple variants, encoding distinct isoforms, are described. Additional splice variation has been identified but the full-length nature of these transcripts has not been determined. [provided by RefSeq, Jun 2013]

LARP1B links:

LARP1B (HGNC:):

LARP1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP1B	NM_018078.4 linkuse as main transcript	c.672A>C	p.Glu224Asp	missense_variant	8/20	ENST00000326639.11	NP_060548.2	Q659C4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP1B	ENST00000326639.11 linkuse as main transcript	c.672A>C	p.Glu224Asp	missense_variant	8/20	5	NM_018078.4	ENSP00000321997.6		Q659C4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250900

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1453332

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723456

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000362

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 20, 2022

The c.672A>C (p.E224D) alteration is located in exon 8 (coding exon 6) of the LARP1B gene. This alteration results from a A to C substitution at nucleotide position 672, causing the glutamic acid (E) at amino acid position 224 to be replaced by an aspartic acid (D). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

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

Eigen

Benign

-0.014

Eigen_PC

Benign

-0.098

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.99

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

M_CAP

Benign

0.046

MetaRNN

Pathogenic

0.86

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

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.0

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

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.6

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

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0070

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

Sift4G

Pathogenic

0.0

D;D;D;T;T;.;.;.

Polyphen

1.0

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

Vest4

0.83

MutPred

0.83

Gain of glycosylation at Y226 (P = 0.0591);Gain of glycosylation at Y226 (P = 0.0591);.;Gain of glycosylation at Y226 (P = 0.0591);Gain of glycosylation at Y226 (P = 0.0591);.;.;.;

MVP

0.63

MPC

0.62

ClinPred

0.92

GERP RS

-0.14

Varity_R

0.42

gMVP

0.79

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

Other links and lift over