1-200908890-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142569.3(INAVA):c.735C>A(p.Asp245Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: INAVA NM_001142569.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.615

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2731189).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INAVA	NM_001142569.3	c.735C>A	p.Asp245Glu	missense_variant	7/10	ENST00000413687.3
INAVA	NM_018265.4	c.990C>A	p.Asp330Glu	missense_variant	7/10
INAVA	NM_001367289.1	c.735C>A	p.Asp245Glu	missense_variant	7/10
INAVA	NM_001367290.1	c.198C>A	p.Asp66Glu	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INAVA	ENST00000413687.3	c.735C>A	p.Asp245Glu	missense_variant	7/10	2	NM_001142569.3	P2
INAVA	ENST00000367342.8	c.1032C>A	p.Asp344Glu	missense_variant	7/10	1		A2
INAVA	ENST00000526172.1	n.216C>A		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.1032C>A (p.D344E) alteration is located in exon 7 (coding exon 7) of the C1orf106 gene. This alteration results from a C to A substitution at nucleotide position 1032, causing the aspartic acid (D) at amino acid position 344 to be replaced by a glutamic acid (E). 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	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.054	T;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.076
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.66	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.38	T
MutationTaster	Benign	0.91	D;N
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.055	T;T
Polyphen		1.0	D;.
Vest4		0.43
MutPred		0.21		Gain of solvent accessibility (P = 0.0306);.;
MVP		0.18
MPC		0.58
ClinPred		0.97	D
GERP RS		1.8
Varity_R		0.39
gMVP		0.31

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: chr1-200878018;