NM_001080460.3:c.13A>C

Variant names:

• chr3-169821934-A-C
• rs752420006
• NM_001080460.3:c.13A>C

Variant summary

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

The NM_001080460.3(LRRIQ4):​c.13A>C​(p.Ile5Leu) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRIQ4 NM_001080460.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628
• Publications: 0 publications found

Genes affected

LRRIQ4 (HGNC:34298): (leucine rich repeats and IQ motif containing 4) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Predicted to be active in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

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=0.04589227).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080460.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRIQ4	NM_001080460.3	MANE Select	c.13A>C	p.Ile5Leu	missense	Exon 2 of 6	NP_001073929.1	A6NIV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRIQ4	ENST00000340806.7	TSL:5 MANE Select	c.13A>C	p.Ile5Leu	missense	Exon 2 of 6	ENSP00000342188.6	A6NIV6
	LRRIQ4	ENST00000691416.1		c.13A>C	p.Ile5Leu	missense	Exon 2 of 5	ENSP00000508855.1	A0A8I5KNZ9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1318884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 642980

African (AFR) AF: 0.00 AC: 0 AN: 29130

American (AMR) AF: 0.00 AC: 0 AN: 22986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19102

East Asian (EAS) AF: 0.00 AC: 0 AN: 36346

South Asian (SAS) AF: 0.00 AC: 0 AN: 59132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5154

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1044412

Other (OTH) AF: 0.00 AC: 0 AN: 53956

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.085
DANN	Benign	0.54
DEOGEN2	Benign	0.00064	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N
PhyloP100		-0.63
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.0050
Sift	Benign	0.56	T
Sift4G	Benign	0.94	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.50		Loss of catalytic residue at I5 (P = 0.0016)
MVP		0.061
MPC		0.10
ClinPred		0.039	T
GERP RS		-4.0
Varity_R		0.046
gMVP		0.075
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

dbSNP: rs752420006; hg19: chr3-169539722;