Variant 12-85038211-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001079910.2(LRRIQ1):c.35T>C(p.Ile12Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,429,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

LRRIQ1
NM_001079910.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Variant links:

Genes affected

LRRIQ1 (HGNC:25708): (leucine rich repeats and IQ motif containing 1)

LRRIQ1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3461023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRIQ1	NM_001079910.2 linkuse as main transcript	c.35T>C	p.Ile12Thr	missense_variant	2/27	ENST00000393217.7	NP_001073379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRIQ1	ENST00000393217.7 linkuse as main transcript	c.35T>C	p.Ile12Thr	missense_variant	2/27	1	NM_001079910.2	ENSP00000376910	P1	Q96JM4-4
LRRIQ1	ENST00000529408.1 linkuse as main transcript	n.130T>C		non_coding_transcript_exon_variant	2/6	1
LRRIQ1	ENST00000393212.7 linkuse as main transcript	c.35T>C	p.Ile12Thr	missense_variant	2/6	4		ENSP00000376906
LRRIQ1	ENST00000525971.6 linkuse as main transcript	n.153T>C		non_coding_transcript_exon_variant	2/17	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000429

AC:

AN:

233282

Hom.:

AF XY:

0.00000788

AC XY:

AN XY:

126878

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000935

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1429648

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

711476

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000137

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 12, 2023

The c.35T>C (p.I12T) alteration is located in exon 2 (coding exon 1) of the LRRIQ1 gene. This alteration results from a T to C substitution at nucleotide position 35, causing the isoleucine (I) at amino acid position 12 to be replaced by a threonine (T). 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

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.35

T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.7

.;M

MutationTaster

Benign

0.88

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.97

.;D

Vest4

0.54

MutPred

0.25

Gain of phosphorylation at I12 (P = 0.0298);Gain of phosphorylation at I12 (P = 0.0298);

MVP

0.75

MPC

0.064

ClinPred

0.97

GERP RS

4.9

Varity_R

0.54

gMVP

0.097

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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