1-74026887-G-T

Variant names:

• chr1-74026887-G-T
• rs1653530584
• NM_001105659.2:c.1801C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105659.2(LRRIQ3):​c.1801C>A​(p.Gln601Lys) 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. 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. Q601E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRIQ3 NM_001105659.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.124535024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.1801C>A	p.Gln601Lys	missense_variant	Exon 8 of 8	ENST00000354431.9	NP_001099129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.1801C>A	p.Gln601Lys	missense_variant	Exon 8 of 8	5	NM_001105659.2	ENSP00000346414.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454898 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 723910

African (AFR) AF: 0.00 AC: 0 AN: 33182

American (AMR) AF: 0.00 AC: 0 AN: 44006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39402

South Asian (SAS) AF: 0.00 AC: 0 AN: 85498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108200

Other (OTH) AF: 0.00 AC: 0 AN: 60070

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.0074	T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.51	.;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		0.59
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.025
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.029	D;D
Polyphen		0.80	P;P
Vest4		0.18
MutPred		0.23		Gain of MoRF binding (P = 0.036);Gain of MoRF binding (P = 0.036);
MVP		0.085
MPC		0.0067
ClinPred		0.20	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.025
Mutation Taster		=95/5	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: rs1653530584; hg19: chr1-74492571; COSMIC: COSV63047800;