Genetic Variant NM_001142569.3:c.1429C>A (chr1-200911922-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142569.3(INAVA):c.1429C>A(p.Arg477Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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. R477C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

INAVA
NM_001142569.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.17

Publications

1 publications found

Variant links:

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]

INAVA links:

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ACMG classification

Classification was made for transcript

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=0.15001076).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INAVA	NM_001142569.3	MANE Select	c.1429C>A	p.Arg477Ser	missense	Exon 9 of 10	NP_001136041.1	Q3KP66-3
INAVA	NM_018265.4		c.1684C>A	p.Arg562Ser	missense	Exon 9 of 10	NP_060735.4	Q3KP66-1
INAVA	NM_001367289.1		c.1429C>A	p.Arg477Ser	missense	Exon 9 of 10	NP_001354218.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INAVA	ENST00000413687.3	TSL:2 MANE Select	c.1429C>A	p.Arg477Ser	missense	Exon 9 of 10	ENSP00000392105.2	Q3KP66-3
INAVA	ENST00000367342.8	TSL:1	c.1726C>A	p.Arg576Ser	missense	Exon 9 of 10	ENSP00000356311.5	A0A8V8N8P9
INAVA	ENST00000877560.1		c.1429C>A	p.Arg477Ser	missense	Exon 9 of 10	ENSP00000547619.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

187552

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1422196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705714

African (AFR)

AF:

0.00

AC:

AN:

32722

American (AMR)

AF:

0.00

AC:

AN:

40844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25542

East Asian (EAS)

AF:

0.00

AC:

AN:

38098

South Asian (SAS)

AF:

0.00

AC:

AN:

82948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4324

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099610

Other (OTH)

AF:

0.00

AC:

AN:

58998

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.018

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

PhyloP100

5.2

PROVEAN

Benign

-1.8

REVEL

Benign

0.091

Sift

Benign

0.19

Sift4G

Benign

0.28

Polyphen

0.21

Vest4

0.38

MVP

0.043

MPC

2.0

ClinPred

0.84

GERP RS

4.3

Varity_R

0.19

gMVP

0.64

Mutation Taster

=91/9

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over