5-64213847-A-G

Variant names:

• chr5-64213847-A-G
• NM_001113561.2:c.521A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001113561.2(RNF180):​c.521A>G​(p.Asp174Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF180 NM_001113561.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0640
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02427715).
• BP6: Variant 5-64213847-A-G is Benign according to our data. Variant chr5-64213847-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3155204.Status of the report is criteria_provided_single_submitter, 1 stars.

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.521A>G	p.Asp174Gly	missense	Exon 4 of 8	NP_001107033.1	Q86T96-1
	RNF180	NM_001323292.2		c.521A>G	p.Asp174Gly	missense	Exon 4 of 7	NP_001310221.1
	RNF180	NM_178532.4		c.521A>G	p.Asp174Gly	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.521A>G	p.Asp174Gly	missense	Exon 4 of 8	ENSP00000373752.4	Q86T96-1
	RNF180	ENST00000296615.10	TSL:1	c.521A>G	p.Asp174Gly	missense	Exon 4 of 5	ENSP00000296615.6	Q86T96-2
	RNF180	ENST00000876163.1		c.521A>G	p.Asp174Gly	missense	Exon 4 of 8	ENSP00000546222.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.75
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.064
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.055
Sift	Benign	1.0	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.22		Gain of MoRF binding (P = 0.0474)
MVP		0.29
MPC		0.040
ClinPred		0.033	T
GERP RS		1.8
Varity_R		0.054
gMVP		0.18
Mutation Taster		=90/10	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

hg19: chr5-63509674;