NM_001105659.2:c.1573C>G

Variant names:

• chr1-74041358-G-C
• rs78197692
• NM_001105659.2:c.1573C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001105659.2(LRRIQ3):​c.1573C>G​(p.Arg525Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 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. R525C) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRIQ3 NM_001105659.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41
• Publications: 4 publications found

Genes affected

LRRIQ3 (HGNC:28318): (leucine rich repeats and IQ motif containing 3)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.1573C>G	p.Arg525Gly	missense_variant	Exon 7 of 8	ENST00000354431.9	NP_001099129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.1573C>G	p.Arg525Gly	missense_variant	Exon 7 of 8	5	NM_001105659.2	ENSP00000346414.4
LRRIQ3	ENST00000395089.5	c.1573C>G	p.Arg525Gly	missense_variant	Exon 6 of 7	5		ENSP00000378524.1
LRRIQ3	ENST00000417067.5	c.131-14389C>G		intron_variant	Intron 1 of 1	2		ENSP00000390376.1
LRRIQ3	ENST00000415760.5	n.*2703+333C>G		intron_variant	Intron 9 of 9	2		ENSP00000415319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PhyloP100		3.4
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0090	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;D
Vest4		0.56
MutPred		0.56		Loss of MoRF binding (P = 0.0436);Loss of MoRF binding (P = 0.0436);
MVP		0.30
MPC		0.011
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.10
gMVP		0.030
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs78197692; hg19: chr1-74507042; COSMIC: COSV63043698;