NM_001128922.2:c.1559A>T

Variant names:

• chr11-76660034-T-A
• NM_001128922.2:c.1559A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001128922.2(LRRC32):​c.1559A>T​(p.Asn520Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N520S) has been classified 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: 5.95
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• cleft palate, proliferative retinopathy, and developmental delay

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LRRC32-AS1 (HGNC:58233):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128922.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC32	NM_001128922.2	MANE Select	c.1559A>T	p.Asn520Ile	missense	Exon 3 of 3	NP_001122394.1	Q14392
	LRRC32	NM_001370187.1		c.1559A>T	p.Asn520Ile	missense	Exon 3 of 4	NP_001357116.1	Q14392
	LRRC32	NM_001370188.1		c.1559A>T	p.Asn520Ile	missense	Exon 3 of 4	NP_001357117.1	Q14392

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC32	ENST00000260061.9	TSL:1 MANE Select	c.1559A>T	p.Asn520Ile	missense	Exon 3 of 3	ENSP00000260061.5	Q14392
	LRRC32	ENST00000407242.6	TSL:1	c.1559A>T	p.Asn520Ile	missense	Exon 3 of 3	ENSP00000384126.2	Q14392
	LRRC32-AS1	ENST00000447519.2	TSL:1	n.260+340T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.61		Gain of ubiquitination at K517 (P = 0.0725)
MVP		0.81
MPC		0.77
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.80
gMVP		0.95
Mutation Taster		=36/64	disease causing

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

Other links and lift over

hg19: chr11-76371078;