Genetic Variant LRRC32:p.Ala531Val (chr11-76660001-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001128922.2(LRRC32):c.1592C>T(p.Ala531Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LRRC32
NM_001128922.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

Variant links:

Genes affected

LRRC32 (HGNC:4161): (leucine rich repeat containing 32) This gene encodes a type I membrane protein which contains 20 leucine-rich repeats. Alterations in the chromosomal region 11q13-11q14 are involved in several pathologies. [provided by RefSeq, Jul 2008]

LRRC32 links:

ENSG00000236304 (HGNC:58233):

ENSG00000236304 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32463604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC32	NM_001128922.2 link	c.1592C>T	p.Ala531Val	missense_variant	Exon 3 of 3	ENST00000260061.9	NP_001122394.1	Q14392A0A024R5J7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC32	ENST00000260061.9 link	c.1592C>T	p.Ala531Val	missense_variant	Exon 3 of 3	1	NM_001128922.2	ENSP00000260061.5		Q14392

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727190

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1592C>T (p.A531V) alteration is located in exon 3 (coding exon 2) of the LRRC32 gene. This alteration results from a C to T substitution at nucleotide position 1592, causing the alanine (A) at amino acid position 531 to be replaced by a valine (V). 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

0.095

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.056

T;T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.79

.;T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.31

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.96

D;D;D

Vest4

0.18

MutPred

0.48

Loss of catalytic residue at A531 (P = 0.0297);Loss of catalytic residue at A531 (P = 0.0297);Loss of catalytic residue at A531 (P = 0.0297);

MVP

0.93

MPC

0.34

ClinPred

0.65

GERP RS

4.3

Varity_R

0.063

gMVP

0.88

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over