3-169822112-C-T

Variant names:

• chr3-169822112-C-T
• rs1409956519
• NM_001080460.3:c.191C>T

Variant summary

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

The NM_001080460.3(LRRIQ4):​c.191C>T​(p.Pro64Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: LRRIQ4 NM_001080460.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

Genes affected

LRRIQ4 (HGNC:34298): (leucine rich repeats and IQ motif containing 4) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Predicted to be active in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

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
LRRIQ4	NM_001080460.3	c.191C>T	p.Pro64Leu	missense_variant	Exon 2 of 6	ENST00000340806.7	NP_001073929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRIQ4	ENST00000340806.7	c.191C>T	p.Pro64Leu	missense_variant	Exon 2 of 6	5	NM_001080460.3	ENSP00000342188.6
LRRIQ4	ENST00000691416.1	c.191C>T	p.Pro64Leu	missense_variant	Exon 2 of 5			ENSP00000508855.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74324

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000224 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.191C>T (p.P64L) alteration is located in exon 1 (coding exon 1) of the LRRIQ4 gene. This alteration results from a C to T substitution at nucleotide position 191, causing the proline (P) at amino acid position 64 to be replaced by a leucine (L). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.46
MutPred		0.63		Loss of disorder (P = 0.0303);
MVP		0.71
MPC		0.52
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.51
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs1409956519; hg19: chr3-169539900;