NM_001080460.3:c.293G>C

Variant names:

• chr3-169822214-G-C
• rs371218215
• NM_001080460.3:c.293G>C

Variant summary

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

The NM_001080460.3(LRRIQ4):​c.293G>C​(p.Ser98Thr) 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. 17/22 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. S98I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRIQ4 NM_001080460.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 1 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: 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=0.17185745).

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.293G>C	p.Ser98Thr	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.293G>C	p.Ser98Thr	missense	Exon 2 of 6	ENSP00000342188.6	A6NIV6
	LRRIQ4	ENST00000691416.1		c.293G>C	p.Ser98Thr	missense	Exon 2 of 5	ENSP00000508855.1	A0A8I5KNZ9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.053
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	N
PhyloP100		1.6
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.11
Sift	Benign	0.59	T
Sift4G	Benign	0.35	T
Polyphen		0.89	P
Vest4		0.083
MutPred		0.32		Loss of disorder (P = 0.0501)
MVP		0.41
MPC		0.40
ClinPred		0.36	T
GERP RS		4.8
Varity_R		0.053
gMVP		0.39
Mutation Taster		=97/3	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: rs371218215; hg19: chr3-169540002;