chr3-169822526-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080460.3(LRRIQ4):​c.605C>G​(p.Ala202Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A202V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

LRRIQ4
NM_001080460.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.87
Variant links:
Genes affected
LRRIQ4 (HGNC:34298): (leucine rich repeats and IQ motif containing 4) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Predicted to be active in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10103428).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRIQ4NM_001080460.3 linkc.605C>G p.Ala202Gly missense_variant Exon 2 of 6 ENST00000340806.7 NP_001073929.1 A6NIV6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRIQ4ENST00000340806.7 linkc.605C>G p.Ala202Gly missense_variant Exon 2 of 6 5 NM_001080460.3 ENSP00000342188.6 A6NIV6
LRRIQ4ENST00000691416.1 linkc.605C>G p.Ala202Gly missense_variant Exon 2 of 5 ENSP00000508855.1 A0A8I5KNZ9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
249020
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135100
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:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461604
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727064
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113
ExAC
AF:
0.00000828
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.605C>G (p.A202G) alteration is located in exon 1 (coding exon 1) of the LRRIQ4 gene. This alteration results from a C to G substitution at nucleotide position 605, causing the alanine (A) at amino acid position 202 to be replaced by a glycine (G). 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
0.10
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.12
DANN
Benign
0.94
DEOGEN2
Benign
0.010
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.047
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.95
L
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.0080
Sift
Benign
0.092
T
Sift4G
Benign
0.36
T
Polyphen
0.27
B
Vest4
0.14
MutPred
0.35
Gain of disorder (P = 0.0411);
MVP
0.048
MPC
0.28
ClinPred
0.23
T
GERP RS
-2.6
Varity_R
0.050
gMVP
0.063

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.

Other links and lift over

dbSNP: rs758789510; hg19: chr3-169540314; API