11-76660038-G-A

Variant names:

• chr11-76660038-G-A
• NM_001128922.2:c.1555C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001128922.2(LRRC32):​c.1555C>T​(p.Leu519Phe) 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 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC32 NM_001128922.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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:58233):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC32	NM_001128922.2	c.1555C>T	p.Leu519Phe	missense_variant	Exon 3 of 3	ENST00000260061.9	NP_001122394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC32	ENST00000260061.9	c.1555C>T	p.Leu519Phe	missense_variant	Exon 3 of 3	1	NM_001128922.2	ENSP00000260061.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727186

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1555C>T (p.L519F) 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 1555, causing the leucine (L) at amino acid position 519 to be replaced by a phenylalanine (F). 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	0.79
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.77	.;T;.
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Uncertain	2.9	M;M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0070	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.36
MutPred		0.65		Gain of ubiquitination at K517 (P = 0.0804);Gain of ubiquitination at K517 (P = 0.0804);Gain of ubiquitination at K517 (P = 0.0804);
MVP		0.96
MPC		0.73
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.35
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-76371082;