Variant chr1-74041242-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001105659.2(LRRIQ3):c.1689G>T(p.Lys563Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,585,446 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

LRRIQ3
NM_001105659.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.687

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027425855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRIQ3	NM_001105659.2 linkuse as main transcript	c.1689G>T	p.Lys563Asn	missense_variant	7/8	ENST00000354431.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRIQ3	ENST00000354431.9 linkuse as main transcript	c.1689G>T	p.Lys563Asn	missense_variant	7/8	5	NM_001105659.2	P2	A6PVS8-1
LRRIQ3	ENST00000395089.5 linkuse as main transcript	c.1689G>T	p.Lys563Asn	missense_variant	6/7	5		P2	A6PVS8-1
LRRIQ3	ENST00000417067.5 linkuse as main transcript	c.131-14273G>T		intron_variant		2
LRRIQ3	ENST00000415760.5 linkuse as main transcript	c.*2703+449G>T		intron_variant, NMD_transcript_variant		2			A6PVS8-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000192

AC:

AN:

228596

Hom.:

AF XY:

0.000202

AC XY:

AN XY:

123988

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000683

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000609

Gnomad SAS exome

AF:

0.000783

Gnomad FIN exome

AF:

0.0000478

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.000367

GnomAD4 exome

AF:

0.000170

AC:

243

AN:

1433408

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

127

AN XY:

712124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000517

Gnomad4 ASJ exome

AF:

0.0000400

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000636

Gnomad4 FIN exome

AF:

0.0000567

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.000203

GnomAD4 genome

AF:

0.000105

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000224

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.000384

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.1689G>T (p.K563N) alteration is located in exon 7 (coding exon 6) of the LRRIQ3 gene. This alteration results from a G to T substitution at nucleotide position 1689, causing the lysine (K) at amino acid position 563 to be replaced by an asparagine (N). 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

0.26

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0025

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.058

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.93

P;P

Vest4

0.10

MutPred

0.15

Loss of methylation at K563 (P = 0.0427);Loss of methylation at K563 (P = 0.0427);

MVP

0.092

MPC

0.0040

ClinPred

0.043

GERP RS

3.9

Varity_R

0.13

gMVP

0.026

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over