dbSNP rs774469314: LRRIQ3:p.Ile479Val (chr1-74041496-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001105659.2(LRRIQ3):c.1435A>G(p.Ile479Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,046 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I479L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LRRIQ3
NM_001105659.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07127744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2 link	c.1435A>G	p.Ile479Val	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.1435A>G	p.Ile479Val	missense_variant	Exon 7 of 8	5	NM_001105659.2	ENSP00000346414.4	A6PVS8-1
LRRIQ3	ENST00000395089.5 link	c.1435A>G	p.Ile479Val	missense_variant	Exon 6 of 7	5		ENSP00000378524.1	A6PVS8-1
LRRIQ3	ENST00000417067.5 link	c.131-14527A>G		intron_variant	Intron 1 of 1	2		ENSP00000390376.1	A6PVT2
LRRIQ3	ENST00000415760.5 link	n.*2703+195A>G		intron_variant	Intron 9 of 9	2		ENSP00000415319.1	A6PVS8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

247166

AF XY:

0.00000746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460046

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726254

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33272

American (AMR)

AF:

0.00

AC:

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

85750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111600

Other (OTH)

AF:

0.00

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.34

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.32

.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.65

N;N

PhyloP100

0.15

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.25

N;N

REVEL

Benign

0.040

Sift

Benign

0.098

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0070

B;B

Vest4

0.074

MutPred

0.53

Gain of disorder (P = 0.112);Gain of disorder (P = 0.112);

MVP

0.040

MPC

0.0045

ClinPred

0.081

GERP RS

0.79

Varity_R

0.028

gMVP

0.014

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over