1-74026887-G-C

Position:

• chr1-74026887-G-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.1801C>G​(p.Gln601Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,898 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LRRIQ3 NM_001105659.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.590

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=0.058916092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRIQ3	NM_001105659.2	c.1801C>G	p.Gln601Glu	missense_variant	8/8	ENST00000354431.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.1801C>G	p.Gln601Glu	missense_variant	8/8	5	NM_001105659.2	P2
LRRIQ3	ENST00000395089.5	c.1801C>G	p.Gln601Glu	missense_variant	7/7	5		P2
LRRIQ3	ENST00000417067.5	c.*30C>G		3_prime_UTR_variant	2/2	2
LRRIQ3	ENST00000415760.5	c.*2786C>G		3_prime_UTR_variant, NMD_transcript_variant	10/10	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454898 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723910

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: 0.00

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Feb 05, 2024

The c.1801C>G (p.Q601E) alteration is located in exon 8 (coding exon 7) of the LRRIQ3 gene. This alteration results from a C to G substitution at nucleotide position 1801, causing the glutamine (Q) at amino acid position 601 to be replaced by a glutamic acid (E). 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	0.082
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.36
DEOGEN2	Benign	0.0012	T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.79	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.85	N;N
REVEL	Benign	0.053
Sift	Benign	0.48	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.024	B;B
Vest4		0.074
MVP		0.048
MPC		0.0040
ClinPred		0.049	T
GERP RS		2.9
Varity_R		0.060
gMVP		0.0072

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

Other links and lift over

dbSNP: rs1653530584; hg19: chr1-74492571;