chr1-200900111-C-A

Variant names:

• chr1-200900111-C-A
• rs150962388
• NM_001142569.3:c.188C>A

Variant summary

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

The NM_001142569.3(INAVA):​c.188C>A​(p.Thr63Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,622 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T63M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: INAVA NM_001142569.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02
• Publications: 0 publications found

Genes affected

INAVA (HGNC:25599): (innate immunity activator) Involved in several processes, including nucleotide-binding activity oligomerization domain containing 2 signaling pathway; positive regulation of cytokine production; and positive regulation of intracellular signal transduction. Located in cytoplasm and nucleus. Implicated in inflammatory bowel disease 29. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142569.3. 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
	INAVA	NM_001142569.3	MANE Select	c.188C>A	p.Thr63Lys	missense	Exon 4 of 10	NP_001136041.1	Q3KP66-3
	INAVA	NM_018265.4		c.443C>A	p.Thr148Lys	missense	Exon 4 of 10	NP_060735.4	Q3KP66-1
	INAVA	NM_001367289.1		c.188C>A	p.Thr63Lys	missense	Exon 4 of 10	NP_001354218.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INAVA	ENST00000413687.3	TSL:2 MANE Select	c.188C>A	p.Thr63Lys	missense	Exon 4 of 10	ENSP00000392105.2	Q3KP66-3
	INAVA	ENST00000367342.8	TSL:1	c.485C>A	p.Thr162Lys	missense	Exon 4 of 10	ENSP00000356311.5	A0A8V8N8P9
	INAVA	ENST00000877560.1		c.188C>A	p.Thr63Lys	missense	Exon 4 of 10	ENSP00000547619.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459622 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725922

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 85864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110882

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	0.051	D
PhyloP100		6.0
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.26		Gain of ubiquitination at T148 (P = 0.0077)
MVP		0.68
MPC		0.73
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.87
gMVP		0.91
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150962388; hg19: chr1-200869239;