Variant chr1-74026949-C-T 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.1739G>A(p.Arg580Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 1,566,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 0 hom. )

Consequence

LRRIQ3
NM_001105659.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.135

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=0.022618085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRIQ3	NM_001105659.2 linkuse as main transcript	c.1739G>A	p.Arg580Lys	missense_variant	8/8	ENST00000354431.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRIQ3	ENST00000354431.9 linkuse as main transcript	c.1739G>A	p.Arg580Lys	missense_variant	8/8	5	NM_001105659.2	P2	A6PVS8-1
LRRIQ3	ENST00000395089.5 linkuse as main transcript	c.1739G>A	p.Arg580Lys	missense_variant	7/7	5		P2	A6PVS8-1
LRRIQ3	ENST00000417067.5 linkuse as main transcript	c.151G>A	p.Asp51Asn	missense_variant	2/2	2
LRRIQ3	ENST00000415760.5 linkuse as main transcript	c.*2724G>A		3_prime_UTR_variant, NMD_transcript_variant	10/10	2			A6PVS8-2

Frequencies

GnomAD3 genomes

AF:

0.000415

AC:

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.000795

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000343

AC:

AN:

233214

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

127026

show subpopulations

Gnomad AFR exome

AF:

0.0000666

Gnomad AMR exome

AF:

0.000168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000199

Gnomad NFE exome

AF:

0.000625

Gnomad OTH exome

AF:

0.000353

GnomAD4 exome

AF:

0.000635

AC:

899

AN:

1414664

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

417

AN XY:

705406

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000195

Gnomad4 NFE exome

AF:

0.000787

Gnomad4 OTH exome

AF:

0.000426

GnomAD4 genome

AF:

0.000414

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000795

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000672

Hom.:

Bravo

AF:

0.000446

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000370

AC:

ExAC

AF:

0.000365

AC:

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

Oct 18, 2021

The c.1739G>A (p.R580K) alteration is located in exon 8 (coding exon 7) of the LRRIQ3 gene. This alteration results from a G to A substitution at nucleotide position 1739, causing the arginine (R) at amino acid position 580 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.0

DANN

Benign

0.65

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.36

M_CAP

Benign

0.0057

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

N;N

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.12

Sift

Pathogenic

0.0

MVP

0.040

ClinPred

0.016

GERP RS

-1.2

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

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