1-74041336-A-T

Variant names:

• chr1-74041336-A-T
• rs770094440
• NM_001105659.2:c.1595T>A

Variant summary

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

The NM_001105659.2(LRRIQ3):​c.1595T>A​(p.Leu532Gln) variant causes a missense change. 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. L532R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRIQ3 NM_001105659.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65
• Publications: 0 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.1595T>A	p.Leu532Gln	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.1595T>A	p.Leu532Gln	missense_variant	Exon 7 of 8	5	NM_001105659.2	ENSP00000346414.4
LRRIQ3	ENST00000395089.5	c.1595T>A	p.Leu532Gln	missense_variant	Exon 6 of 7	5		ENSP00000378524.1
LRRIQ3	ENST00000417067.5	c.131-14367T>A		intron_variant	Intron 1 of 1	2		ENSP00000390376.1
LRRIQ3	ENST00000415760.5	n.*2703+355T>A		intron_variant	Intron 9 of 9	2		ENSP00000415319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0047	T;T
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.45	.;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
PhyloP100		4.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.93	P;P
Vest4		0.59
MutPred		0.46		Loss of catalytic residue at L532 (P = 0.011);Loss of catalytic residue at L532 (P = 0.011);
MVP		0.29
MPC		0.013
ClinPred		0.71	D
GERP RS		5.9
Varity_R		0.16
gMVP		0.037
Mutation Taster		=94/6	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: rs770094440; hg19: chr1-74507020;