Genetic Variant LRRIQ3:p.Ile551Val (chr1-74041280-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001105659.2(LRRIQ3):c.1651A>G(p.Ile551Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LRRIQ3
NM_001105659.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.164

Publications

0 publications found

Variant links:

Genes affected

LRRIQ3 (HGNC:28318): (leucine rich repeats and IQ motif containing 3)

LRRIQ3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044360876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2 link	c.1651A>G	p.Ile551Val	missense_variant	Exon 7 of 8	ENST00000354431.9	NP_001099129.1	A6PVS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRRIQ3	ENST00000354431.9 link	c.1651A>G	p.Ile551Val	missense_variant	Exon 7 of 8	5	NM_001105659.2	ENSP00000346414.4	A6PVS8-1
LRRIQ3	ENST00000395089.5 link	c.1651A>G	p.Ile551Val	missense_variant	Exon 6 of 7	5		ENSP00000378524.1	A6PVS8-1
LRRIQ3	ENST00000417067.5 link	c.131-14311A>G		intron_variant	Intron 1 of 1	2		ENSP00000390376.1	A6PVT2
LRRIQ3	ENST00000415760.5 link	n.*2703+411A>G		intron_variant	Intron 9 of 9	2		ENSP00000415319.1	A6PVS8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721902

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32902

American (AMR)

AF:

0.00

AC:

AN:

42886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25770

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

82684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109920

Other (OTH)

AF:

0.00

AC:

AN:

60012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1651A>G (p.I551V) alteration is located in exon 7 (coding exon 6) of the LRRIQ3 gene. This alteration results from a A to G substitution at nucleotide position 1651, causing the isoleucine (I) at amino acid position 551 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

0.092

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.36

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.0014

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.34

.;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

L;L

PhyloP100

-0.16

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.011

Sift

Benign

0.074

T;T

Sift4G

Benign

0.75

T;T

Polyphen

0.0060

B;B

Vest4

0.070

MutPred

0.16

Gain of ubiquitination at K546 (P = 0.1008);Gain of ubiquitination at K546 (P = 0.1008);

MVP

0.014

MPC

0.0045

ClinPred

0.098

GERP RS

-6.0

Varity_R

0.023

gMVP

0.0047

Mutation Taster

=100/0

polymorphism

(source)

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

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chr1-74041280-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over