Variant chr15-70853965-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018357.4(LARP6):c.124G>C(p.Gly42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000788 in 1,457,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00080 ( 0 hom. )

Consequence

LARP6
NM_018357.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0120

Variant links:

Genes affected

LARP6 (HGNC:24012): (La ribonucleoprotein 6, translational regulator) Enables RNA binding activity and myosin binding activity. Involved in positive regulation of collagen biosynthetic process; positive regulation of mRNA binding activity; and positive regulation of translation. Located in nucleus. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

LARP6 links:

LRRC49 (HGNC:25965): (leucine rich repeat containing 49) Predicted to be involved in outer dynein arm assembly. Predicted to be located in microtubule. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRRC49 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011440903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LARP6	NM_018357.4 linkuse as main transcript	c.124G>C	p.Gly42Arg	missense_variant	1/3	ENST00000299213.10
LARP6	NM_197958.3 linkuse as main transcript	c.124G>C	p.Gly42Arg	missense_variant	1/2
LRRC49	NM_001284357.2 linkuse as main transcript	c.-299+496C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARP6	ENST00000299213.10 linkuse as main transcript	c.124G>C	p.Gly42Arg	missense_variant	1/3	1	NM_018357.4	P1	Q9BRS8-1

Frequencies

GnomAD3 genomes

AF:

0.000706

AC:

107

AN:

151590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00158

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000885

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.000621

AC:

AN:

87000

Hom.:

AF XY:

0.000613

AC XY:

AN XY:

48964

show subpopulations

Gnomad AFR exome

AF:

0.000669

Gnomad AMR exome

AF:

0.000924

Gnomad ASJ exome

AF:

0.000753

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000439

GnomAD4 exome

AF:

0.000798

AC:

1042

AN:

1306176

Hom.:

Cov.:

AF XY:

0.000778

AC XY:

501

AN XY:

644160

show subpopulations

Gnomad4 AFR exome

AF:

0.000113

Gnomad4 AMR exome

AF:

0.000930

Gnomad4 ASJ exome

AF:

0.000934

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000137

Gnomad4 NFE exome

AF:

0.000914

Gnomad4 OTH exome

AF:

0.000756

GnomAD4 genome

AF:

0.000705

AC:

107

AN:

151698

Hom.:

Cov.:

AF XY:

0.000688

AC XY:

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00158

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000192

Gnomad4 NFE

AF:

0.000885

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.000761

Hom.:

Bravo

AF:

0.000850

ESP6500AA

AF:

0.000625

AC:

ESP6500EA

AF:

0.000489

AC:

ExAC

AF:

0.000126

AC:

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

Aug 13, 2021

The c.124G>C (p.G42R) alteration is located in exon 1 (coding exon 1) of the LARP6 gene. This alteration results from a G to C substitution at nucleotide position 124, causing the glycine (G) at amino acid position 42 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

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.62

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.22

N;D

REVEL

Benign

0.081

Sift

Uncertain

0.014

D;D

Sift4G

Benign

0.064

T;D

Polyphen

0.093

B;.

Vest4

0.079

MVP

0.15

MPC

0.56

ClinPred

0.020

GERP RS

3.2

Varity_R

0.15

gMVP

0.14

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