Variant 1-100155081-G-T 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_144620.4(LRRC39):c.782C>A(p.Pro261Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,598,666 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: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

LRRC39
NM_144620.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.20

Variant links:

Genes affected

LRRC39 (HGNC:28228): (leucine rich repeat containing 39) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Predicted to be located in M band. Predicted to be active in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LRRC39 links:

Genome browser will be placed here

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, 0.908

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC39	NM_144620.4 linkuse as main transcript	c.782C>A	p.Pro261Gln	missense_variant	8/10	ENST00000370137.6	NP_653221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC39	ENST00000370137.6 linkuse as main transcript	c.782C>A	p.Pro261Gln	missense_variant	8/10	1	NM_144620.4	ENSP00000359156	P1	Q96DD0-1
LRRC39	ENST00000370138.1 linkuse as main transcript	c.782C>A	p.Pro261Gln	missense_variant	8/11	5		ENSP00000359157		Q96DD0-2
LRRC39	ENST00000342895.8 linkuse as main transcript	c.782C>A	p.Pro261Gln	missense_variant	8/10	5		ENSP00000344470	P1	Q96DD0-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000294

AC:

AN:

237950

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128666

show subpopulations

Gnomad AFR exome

AF:

0.000447

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1446582

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

719286

show subpopulations

Gnomad4 AFR exome

AF:

0.000709

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:

0.00000181

Gnomad4 OTH exome

AF:

0.0000670

GnomAD4 genome

AF:

0.000158

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.000556

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000500

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Jun 03, 2024

The c.782C>A (p.P261Q) alteration is located in exon 8 (coding exon 6) of the LRRC39 gene. This alteration results from a C to A substitution at nucleotide position 782, causing the proline (P) at amino acid position 261 to be replaced by a glutamine (Q). 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

0.83

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

.;T;T;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.97

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

.;.;D;D

M_CAP

Benign

0.028

MetaRNN

Pathogenic

0.91

D;D;D;D

MetaSVM

Uncertain

0.34

MutationAssessor

Pathogenic

3.8

H;H;H;H

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-6.9

.;D;D;D

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.93

MVP

0.92

MPC

0.31

ClinPred

0.97

GERP RS

5.9

Varity_R

0.83

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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