Variant 1-100152458-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144620.4(LRRC39):c.879T>A(p.Asp293Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LRRC39
NM_144620.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0360

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07473749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC39	NM_144620.4 linkuse as main transcript	c.879T>A	p.Asp293Glu	missense_variant	9/10	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.879T>A	p.Asp293Glu	missense_variant	9/10	1	NM_144620.4	ENSP00000359156	P1	Q96DD0-1
LRRC39	ENST00000370138.1 linkuse as main transcript	c.879T>A	p.Asp293Glu	missense_variant	9/11	5		ENSP00000359157		Q96DD0-2
LRRC39	ENST00000342895.8 linkuse as main transcript	c.879T>A	p.Asp293Glu	missense_variant	9/10	5		ENSP00000344470	P1	Q96DD0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251396

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135872

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

May 23, 2024

The c.879T>A (p.D293E) alteration is located in exon 9 (coding exon 7) of the LRRC39 gene. This alteration results from a T to A substitution at nucleotide position 879, causing the aspartic acid (D) at amino acid position 293 to be replaced by a glutamic acid (E). 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

0.067

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.1

DANN

Benign

0.66

DEOGEN2

Benign

0.0052

.;T;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.57

.;.;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.075

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

N;N;N;N

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Benign

0.30

PROVEAN

Benign

0.48

.;N;N;N

REVEL

Benign

0.013

Sift

Benign

1.0

.;T;T;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.0020

B;B;B;B

Vest4

0.15

MutPred

0.32

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.34

MPC

0.043

ClinPred

0.047

GERP RS

2.1

Varity_R

0.039

gMVP

0.20

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