Variant chr3-169851760-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_024727.4(LRRC31):c.1018C>A(p.Leu340Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LRRC31
NM_024727.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

LRRC31 (HGNC:26261): (leucine rich repeat containing 31)

LRRC31 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, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC31	NM_024727.4 linkuse as main transcript	c.1018C>A	p.Leu340Ile	missense_variant	7/9	ENST00000316428.10	NP_079003.2	Q6UY01-1A0A384N629

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC31	ENST00000316428.10 linkuse as main transcript	c.1018C>A	p.Leu340Ile	missense_variant	7/9	1	NM_024727.4	ENSP00000325978.5	Q6UY01-1
LRRC31	ENST00000523069.1 linkuse as main transcript	c.1018C>A	p.Leu340Ile	missense_variant	7/9	1		ENSP00000429145.1	Q6UY01-4
LRRC31	ENST00000264676.9 linkuse as main transcript	c.850C>A	p.Leu284Ile	missense_variant	6/8	2		ENSP00000264676.5	Q6UY01-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249528

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

0.000165

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 25, 2024

The c.1018C>A (p.L340I) alteration is located in exon 8 (coding exon 7) of the LRRC31 gene. This alteration results from a C to A substitution at nucleotide position 1018, causing the leucine (L) at amino acid position 340 to be replaced by an isoleucine (I). 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

0.17

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

T;.;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.068

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Uncertain

0.44

MutationAssessor

Pathogenic

3.2

M;.;M

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.9

N;N;N

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.022

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.58

MutPred

0.77

Gain of catalytic residue at L345 (P = 0.0658);.;Gain of catalytic residue at L345 (P = 0.0658);

MVP

0.85

MPC

0.23

ClinPred

0.94

GERP RS

3.9

Varity_R

0.58

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 26

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