11-76660081-C-A

Position:

• chr11-76660081-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001128922.2(LRRC32):​c.1512G>T​(p.Met504Ile) 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: 33)
• Consequence: LRRC32 NM_001128922.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.788

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]

ENSG00000236304 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047141105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC32	NM_001128922.2	c.1512G>T	p.Met504Ile	missense_variant	3/3	ENST00000260061.9	NP_001122394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC32	ENST00000260061.9	c.1512G>T	p.Met504Ile	missense_variant	3/3	1	NM_001128922.2	ENSP00000260061.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.1512G>T (p.M504I) alteration is located in exon 3 (coding exon 2) of the LRRC32 gene. This alteration results from a G to T substitution at nucleotide position 1512, causing the methionine (M) at amino acid position 504 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	0.14
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.87
DANN	Benign	0.82
DEOGEN2	Benign	0.025	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.34	.;T;.
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.025	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.58	N;N;N
REVEL	Benign	0.042
Sift	Benign	0.52	T;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.050
MutPred		0.50		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.29
MPC		0.19
ClinPred		0.034	T
GERP RS		-6.3
Varity_R		0.041
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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.

Other links and lift over

hg19: chr11-76371125;