Variant 1-53962338-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001256409.2(LRRC42):c.856C>T(p.Leu286Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,461,842 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: 0.000019 ( 0 hom. )

Consequence

LRRC42
NM_001256409.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

LRRC42 (HGNC:28792): (leucine rich repeat containing 42)

LRRC42 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC42	NM_001256409.2 linkuse as main transcript	c.856C>T	p.Leu286Phe	missense_variant	7/9	ENST00000371370.8	NP_001243338.1
LRRC42	NM_052940.5 linkuse as main transcript	c.856C>T	p.Leu286Phe	missense_variant	6/8		NP_443172.1
LRRC42	XM_006710328.5 linkuse as main transcript	c.856C>T	p.Leu286Phe	missense_variant	7/9		XP_006710391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRRC42	ENST00000371370.8 linkuse as main transcript	c.856C>T	p.Leu286Phe	missense_variant	7/9	2	NM_001256409.2	ENSP00000360421	P1
LRRC42	ENST00000319223.8 linkuse as main transcript	c.856C>T	p.Leu286Phe	missense_variant	6/8	1		ENSP00000318185	P1
LRRC42	ENST00000713564.1 linkuse as main transcript	c.856C>T	p.Leu286Phe	missense_variant	7/9			ENSP00000518857	P1
LRRC42	ENST00000477905.1 linkuse as main transcript	n.386C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251424

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000252

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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 12, 2022

The c.856C>T (p.L286F) alteration is located in exon 6 (coding exon 5) of the LRRC42 gene. This alteration results from a C to T substitution at nucleotide position 856, causing the leucine (L) at amino acid position 286 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

Benign

0.30

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

.;D

M_CAP

Benign

0.0050

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.18

Sift

Benign

0.052

T;T

Sift4G

Uncertain

0.014

D;D

Polyphen

1.0

D;D

Vest4

0.82

MutPred

0.45

Gain of methylation at K290 (P = 0.0758);Gain of methylation at K290 (P = 0.0758);

MVP

0.56

MPC

0.41

ClinPred

0.71

GERP RS

6.1

Varity_R

0.082

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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