chr6-34590591-C-T

Position:

• chr6-34590591-C-T

Variant summary

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

The NM_024294.4(ILRUN):​c.871G>A​(p.Gly291Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ILRUN NM_024294.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80

Genes affected

ILRUN (HGNC:21215): (inflammation and lipid regulator with UBA-like and NBR1-like domains) This gene encodes a protein with N-terminal ubiquitin-associated (UBA)-like and central neighbor of BRCA1 gene 1 (NBR1)-like domains. The protein acts an inhibitor of antiviral and proinflammatory cytokine transcription and as a regulator of the renin-angiotensin-aldosterone system (RAAS). [provided by RefSeq, Jul 2021]

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/exons	MANE	Protein	UniProt
ILRUN	NM_024294.4	c.871G>A	p.Gly291Arg	missense_variant	5/5	ENST00000374023.8	NP_077270.1
ILRUN	NM_022758.6	c.673G>A	p.Gly225Arg	missense_variant	4/4		NP_073595.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILRUN	ENST00000374023.8	c.871G>A	p.Gly291Arg	missense_variant	5/5	1	NM_024294.4	ENSP00000363135	P1
ILRUN	ENST00000374026.7	c.673G>A	p.Gly225Arg	missense_variant	4/4	2		ENSP00000363138
ILRUN	ENST00000374021.1	c.649G>A	p.Gly217Arg	missense_variant	5/5	3		ENSP00000363133

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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

Sep 01, 2021

The c.871G>A (p.G291R) alteration is located in exon 5 (coding exon 5) of the C6orf106 gene. This alteration results from a G to A substitution at nucleotide position 871, causing the glycine (G) at amino acid position 291 to be replaced by an arginine (R). 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	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.14	N;.;.
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-0.94	N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.90	P;D;.
Vest4		0.70
MutPred		0.33		Loss of ubiquitination at K287 (P = 0.0298);.;.;
MVP		0.59
MPC		0.29
ClinPred		0.82	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr6-34558368;