3-169822520-T-C

Variant names:

• chr3-169822520-T-C
• NM_001080460.3:c.599T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080460.3(LRRIQ4):​c.599T>C​(p.Ile200Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRIQ4 NM_001080460.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46

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

Verdict is Uncertain_significance. Variant got 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
LRRIQ4	NM_001080460.3	c.599T>C	p.Ile200Thr	missense_variant	Exon 2 of 6	ENST00000340806.7	NP_001073929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRIQ4	ENST00000340806.7	c.599T>C	p.Ile200Thr	missense_variant	Exon 2 of 6	5	NM_001080460.3	ENSP00000342188.6
LRRIQ4	ENST00000691416.1	c.599T>C	p.Ile200Thr	missense_variant	Exon 2 of 5			ENSP00000508855.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.599T>C (p.I200T) alteration is located in exon 1 (coding exon 1) of the LRRIQ4 gene. This alteration results from a T to C substitution at nucleotide position 599, causing the isoleucine (I) at amino acid position 200 to be replaced by a threonine (T). 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	0.27
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Uncertain	0.39
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.070	T
Polyphen		0.98	D
Vest4		0.10
MutPred		0.83		Gain of disorder (P = 0.0177);
MVP		0.47
MPC		0.45
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.23
gMVP		0.17

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: chr3-169540308;