chr1-74041515-A-C

Variant names:

• chr1-74041515-A-C
• NM_001105659.2:c.1416T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001105659.2(LRRIQ3):​c.1416T>G​(p.Ile472Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRIQ3 NM_001105659.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0520
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051876366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.1416T>G	p.Ile472Met	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.1416T>G	p.Ile472Met	missense_variant	Exon 7 of 8	5	NM_001105659.2	ENSP00000346414.4
LRRIQ3	ENST00000395089.5	c.1416T>G	p.Ile472Met	missense_variant	Exon 6 of 7	5		ENSP00000378524.1
LRRIQ3	ENST00000417067.5	c.131-14546T>G		intron_variant	Intron 1 of 1	2		ENSP00000390376.1
LRRIQ3	ENST00000415760.5	n.*2703+176T>G		intron_variant	Intron 9 of 9	2		ENSP00000415319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1416T>G (p.I472M) alteration is located in exon 7 (coding exon 6) of the LRRIQ3 gene. This alteration results from a T to G substitution at nucleotide position 1416, causing the isoleucine (I) at amino acid position 472 to be replaced by a methionine (M). 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	0.065
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.81
DEOGEN2	Benign	0.00099	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.29	.;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.83	L;L
PhyloP100		-0.052
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.56	N;N
REVEL	Benign	0.016
Sift	Benign	0.34	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.019	B;B
Vest4		0.058
MutPred		0.23		Gain of disorder (P = 0.0509);Gain of disorder (P = 0.0509);
MVP		0.061
MPC		0.0041
ClinPred		0.19	T
GERP RS		-5.1
Varity_R		0.045
gMVP		0.018
Mutation Taster		=100/0	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

hg19: chr1-74507199;