chr2-85597458-A-G

Position:

• chr2-85597458-A-G

Variant summary

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

The NM_016494.4(RNF181):​c.416A>G​(p.Gln139Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: RNF181 NM_016494.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84

Genes affected

RNF181 (HGNC:28037): (ring finger protein 181) RNF181 binds the integrin alpha-IIb (ITGA2B; MIM 607759)/beta-3 (ITGB3; MIM 173470) complex and has E3 ubiquitin ligase activity (Brophy et al., 2008 [PubMed 18331836]).[supplied by OMIM, Dec 2008]

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	UniProt
RNF181	NM_016494.4	c.416A>G	p.Gln139Arg	missense_variant	5/5	ENST00000306368.9
RNF181	XM_005264359.5	c.457A>G	p.Ser153Gly	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF181	ENST00000306368.9	c.416A>G	p.Gln139Arg	missense_variant	5/5	1	NM_016494.4	P1
RNF181	ENST00000456023.1	c.406A>G	p.Ser136Gly	missense_variant	4/4	3
RNF181	ENST00000441634.5	c.*262A>G		3_prime_UTR_variant	4/4	2
RNF181	ENST00000443647.5	c.*144A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.045	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.58
Sift	Benign	0.13	T
Sift4G	Benign	0.25	T
Polyphen		0.79	P
Vest4		0.55
MutPred		0.25		Loss of ubiquitination at K137 (P = 0.0201);
MVP		0.80
MPC		0.25
ClinPred		0.70	D
GERP RS		5.3
Varity_R		0.18
gMVP		0.83

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: chr2-85824581;