chr6-13977582-C-T

Variant names:

• chr6-13977582-C-T
• rs1245396002
• NM_152737.4:c.463C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152737.4(RNF182):​c.463C>T​(p.Pro155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 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. P155T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF182 NM_152737.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 0 publications found

Genes affected

RNF182 (HGNC:28522): (ring finger protein 182) Enables ubiquitin-protein transferase activity. Involved in protein ubiquitination. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17780489).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152737.4. 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
	RNF182	NM_152737.4	MANE Select	c.463C>T	p.Pro155Ser	missense	Exon 3 of 3	NP_689950.1	Q8N6D2
	RNF182	NM_001165032.2		c.463C>T	p.Pro155Ser	missense	Exon 4 of 4	NP_001158504.1	Q8N6D2
	RNF182	NM_001165033.2		c.463C>T	p.Pro155Ser	missense	Exon 2 of 2	NP_001158505.1	Q8N6D2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF182	ENST00000488300.6	TSL:1 MANE Select	c.463C>T	p.Pro155Ser	missense	Exon 3 of 3	ENSP00000420465.1	Q8N6D2
	RNF182	ENST00000420478.2	TSL:1	c.463C>T	p.Pro155Ser	missense	Exon 2 of 2	ENSP00000419329.1	C9JVS8
	RNF182	ENST00000537388.1	TSL:2	c.463C>T	p.Pro155Ser	missense	Exon 2 of 2	ENSP00000441271.1	Q8N6D2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251260 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.0059
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.28
Sift	Benign	0.33	T
Sift4G	Benign	0.60	T
Polyphen		0.21	B
Vest4		0.065
MutPred		0.25		Gain of disorder (P = 0.062)
MVP		0.89
MPC		0.13
ClinPred		0.26	T
GERP RS		5.0
Varity_R		0.12
gMVP		0.53
Mutation Taster		=79/21	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: rs1245396002; hg19: chr6-13977813;