NM_001113561.2:c.790A>G

Variant names:

• chr5-64214116-A-G
• rs899960454
• NM_001113561.2:c.790A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001113561.2(RNF180):​c.790A>G​(p.Ile264Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. I264F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: RNF180 NM_001113561.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 0 publications found

Genes affected

RNF180 (HGNC:27752): (ring finger protein 180) Predicted to enable ubiquitin conjugating enzyme binding activity and ubiquitin protein ligase activity. Predicted to be involved in norepinephrine metabolic process; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and serotonin metabolic process. Predicted to act upstream of or within several processes, including adult behavior; positive regulation of protein ubiquitination; and protein polyubiquitination. Predicted to be located in nuclear envelope. Predicted to be integral component of membrane. Predicted to be intrinsic component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02657786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113561.2. 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
	RNF180	NM_001113561.2	MANE Select	c.790A>G	p.Ile264Val	missense	Exon 4 of 8	NP_001107033.1	Q86T96-1
	RNF180	NM_001323292.2		c.790A>G	p.Ile264Val	missense	Exon 4 of 7	NP_001310221.1
	RNF180	NM_178532.4		c.790A>G	p.Ile264Val	missense	Exon 4 of 5	NP_848627.1	Q86T96-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF180	ENST00000389100.9	TSL:1 MANE Select	c.790A>G	p.Ile264Val	missense	Exon 4 of 8	ENSP00000373752.4	Q86T96-1
	RNF180	ENST00000296615.10	TSL:1	c.790A>G	p.Ile264Val	missense	Exon 4 of 5	ENSP00000296615.6	Q86T96-2
	RNF180	ENST00000876163.1		c.790A>G	p.Ile264Val	missense	Exon 4 of 8	ENSP00000546222.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461776 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111950

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.43
DEOGEN2	Benign	0.00093	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.56
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.097
Sift	Benign	0.85	T
Sift4G	Benign	0.83	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.20		Gain of phosphorylation at S267 (P = 0.2118)
MVP		0.33
MPC		0.030
ClinPred		0.042	T
GERP RS		-5.3
Varity_R		0.026
gMVP		0.056
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs899960454; hg19: chr5-63509943;