1-74041411-T-C

Position:

• chr1-74041411-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001105659.2(LRRIQ3):​c.1520A>G​(p.Glu507Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRIQ3 NM_001105659.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.173

Genes affected

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

ACMG classification

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=0.057262868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.1520A>G	p.Glu507Gly	missense_variant	7/8	ENST00000354431.9	NP_001099129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.1520A>G	p.Glu507Gly	missense_variant	7/8	5	NM_001105659.2	ENSP00000346414.4
LRRIQ3	ENST00000395089.5	c.1520A>G	p.Glu507Gly	missense_variant	6/7	5		ENSP00000378524.1
LRRIQ3	ENST00000417067.5	c.131-14442A>G		intron_variant		2		ENSP00000390376.1
LRRIQ3	ENST00000415760.5	n.*2703+280A>G		intron_variant		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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2024

The c.1520A>G (p.E507G) alteration is located in exon 7 (coding exon 6) of the LRRIQ3 gene. This alteration results from a A to G substitution at nucleotide position 1520, causing the glutamic acid (E) at amino acid position 507 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	0.085
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0056	T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.37	.;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.048
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.049	B;B
Vest4		0.075
MutPred		0.17		Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP		0.12
MPC		0.0040
ClinPred		0.39	T
GERP RS		2.2
Varity_R		0.076
gMVP		0.038

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-74507095;